The ligand–receptor-based cell-to-cell communication system is one of the most important molecular bases for the establishment of complex multicellular organisms. Plants have evolved highly complex intercellular communication systems. Historical studies have identified several molecules, designated phytohormones, that function in these processes. Recent advances in molecular biological analyses have identified phytohormone receptors and signalling mediators, and have led to the discovery of numerous peptide-based signalling molecules. Subsequent analyses have revealed the involvement in and contribution of these peptides to multiple aspects of the plant life cycle, including development and environmental responses, similar to the functions of canonical phytohormones. On the basis of this knowledge, the view that these peptide hormones are pivotal regulators in plants is becoming increasingly accepted. Peptide hormones are transcribed from the genome and translated into peptides. However, these peptides generally undergo further post-translational modifications to enable them to exert their function. Peptide hormones are expressed in and secreted from specific cells or tissues. Apoplastic peptides are perceived by specialized receptors that are located at the surface of target cells. Peptide hormone–receptor complexes activate intracellular signalling through downstream molecules, including kinases and transcription factors, which then trigger cellular events. In this chapter we provide a comprehensive summary of the biological functions of peptide hormones, focusing on how they mature and the ways in which they modulate plant functions.

Introduction

Multicellular organisms require co-ordinated systems to regulate developmental and physiological processes. Cell-to-cell communication is an important method of ensuring the co-ordination of such processes. Historical studies have demonstrated the importance of various signalling molecules, such as auxin, cytokinins and gibberellins, in establishing cellular communication in plants. These molecules are defined as phytohormones because they are synthesized in plants and facilitate intercellular communication to modulate physiological processes. Over the last 20 years, great advances in molecular biological approaches have led to the discovery of small secreted peptides that function as plant growth factors. To date, numerous peptides have been identified, and their physiological functions in pivotal molecular processes have been elucidated. On the basis of their mode of action, which is analogous to that of the conventional phytohormones, these peptides are considered to be phytohormone-like signalling molecules, and are referred to as ‘peptide hormones’ in this chapter. The concept of peptide hormones is now widely accepted. Therefore we shall review recent advances in research on the physiological aspects of phytohormones and their signalling mediators.

Most peptide hormones contain signal peptide sequences that are cleaved during exocytosis-based secretion and transportation outside the cell. Moreover, the active domain of the mature peptide hormone is excised by proteolytic processing. Some peptide hormones undergo further post-translational modification (e.g. glycosylation, tyrosine sulfation and the formation of disulfide bonds to form their correct stereoscopic structure). When these post-translational modification steps are inhibited, the peptide hormones lose their biological functions. Therefore an understanding of the enzymes that mediate these steps is also important. On the basis of this viewpoint, plant peptide hormones can be grouped into three classes. Class 1 consists of small peptides that undergo proteolytic processing (Figure 1A and Table 1), class 2 contains peptides with disulfide bonds (Figure 1B and Table 1), and class 3 contains peptides that require both processing and disulfide bond formation (Figure 1C and Table 1).

Classification of the plant peptide hormones

Figure 1.
Classification of the plant peptide hormones

On the basis of the view adopted in this review, plant peptide hormones can be grouped into three classes. (A) Class 1 peptide hormones are proteolytically processed to become small active peptides. They sometimes need to be post-translationally modified for full activation. (B) Class 2 peptides require the correct stereoscopic structure for their activity. They are folded through disulfide bonds between their cysteine residues. (C) Class 3 peptides requires both proteolytic processing and disulfide bond formation (C).

Figure 1.
Classification of the plant peptide hormones

On the basis of the view adopted in this review, plant peptide hormones can be grouped into three classes. (A) Class 1 peptide hormones are proteolytically processed to become small active peptides. They sometimes need to be post-translationally modified for full activation. (B) Class 2 peptides require the correct stereoscopic structure for their activity. They are folded through disulfide bonds between their cysteine residues. (C) Class 3 peptides requires both proteolytic processing and disulfide bond formation (C).

Table 1
List of plant peptide hormones described in this review
PeptideModificationProteolytic processingDisulfide bondConserved domainPrimary expressionPrimary receptorBiological function
Class 1 CLE CLV3 Hydroxylation Arabinosylation ✓ – 13 amino acids with two hydroxyproline residues SAM CLV1, CLV2, SOL2/CRN and RPK2 SAM size regulation 
  TDIF Hydroxylation ✓ – 12 amino acids with two hydroxyproline residues Procambial stem cells TDR/PXY Inhibition of xylem differentiation and promotion of procambial cell proliferation 
  RGF Tyrosine sulfation ✓ – 13 amino acids with sulfated tyrosine residue Root meristem – Maintenance of stem cells and root meristem activity 
  PSK Tyrosine sulfation ✓ – Five amino acids with two sulfated tyrosine residues Roots, leaves, stems, flowers, siliques, calluses PSKR Promotion of cell proliferation 
  PSY Tyrosine sulfation Arabinosylation ✓ – 18 amino acids with sulfated tyrosine residue SAM, root meristem, suspension cells PSKR Promotion of cell proliferation 
  CEP Hydroxylation ✓ – 15 amino acids with several hydroxyproline residues Response to nitrare starvation CEPR Induction of nitrate transporters/ modification of root architecture 
  IDA Hydroxylation ✓ – 20 amino acids with two hydroxyproline residues Filaments, sepals, petals during abscission process HAE HSL2 Promotion of floral organ abscission 
Class 2  SCR – – ✓ Six cysteine residues Tapetum, microspore SRK Self recognition on pollination 
  LURE – – ✓ Six cysteine residues Synergid cell – Promotion of pollen tube growth 
Class 3 EPF EPF1/2 – ✓ ✓ – Early stage stomatal lineage cell TMM Regulation of stomata formation 
  STOMAGEN/EPFL9 – ✓ ✓ 45 amino acids with six cysteine residues Mesophyll cell TMM Inhibition of stomata lineage cell fate 
  RALF – ✓ ✓ 49 amino acids with four cysteine residues Root, pollen, ovule, ovary, flower, hypocotyl, leaf, microcalli FER Regulation of extracellular pH and root growth, inhibition of cell elongation 
  ESF1 – ✓ ✓ Six cysteine residues Embryo surrounding micropylar endosperm cells – Regulation of suspensor cell development 
PeptideModificationProteolytic processingDisulfide bondConserved domainPrimary expressionPrimary receptorBiological function
Class 1 CLE CLV3 Hydroxylation Arabinosylation ✓ – 13 amino acids with two hydroxyproline residues SAM CLV1, CLV2, SOL2/CRN and RPK2 SAM size regulation 
  TDIF Hydroxylation ✓ – 12 amino acids with two hydroxyproline residues Procambial stem cells TDR/PXY Inhibition of xylem differentiation and promotion of procambial cell proliferation 
  RGF Tyrosine sulfation ✓ – 13 amino acids with sulfated tyrosine residue Root meristem – Maintenance of stem cells and root meristem activity 
  PSK Tyrosine sulfation ✓ – Five amino acids with two sulfated tyrosine residues Roots, leaves, stems, flowers, siliques, calluses PSKR Promotion of cell proliferation 
  PSY Tyrosine sulfation Arabinosylation ✓ – 18 amino acids with sulfated tyrosine residue SAM, root meristem, suspension cells PSKR Promotion of cell proliferation 
  CEP Hydroxylation ✓ – 15 amino acids with several hydroxyproline residues Response to nitrare starvation CEPR Induction of nitrate transporters/ modification of root architecture 
  IDA Hydroxylation ✓ – 20 amino acids with two hydroxyproline residues Filaments, sepals, petals during abscission process HAE HSL2 Promotion of floral organ abscission 
Class 2  SCR – – ✓ Six cysteine residues Tapetum, microspore SRK Self recognition on pollination 
  LURE – – ✓ Six cysteine residues Synergid cell – Promotion of pollen tube growth 
Class 3 EPF EPF1/2 – ✓ ✓ – Early stage stomatal lineage cell TMM Regulation of stomata formation 
  STOMAGEN/EPFL9 – ✓ ✓ 45 amino acids with six cysteine residues Mesophyll cell TMM Inhibition of stomata lineage cell fate 
  RALF – ✓ ✓ 49 amino acids with four cysteine residues Root, pollen, ovule, ovary, flower, hypocotyl, leaf, microcalli FER Regulation of extracellular pH and root growth, inhibition of cell elongation 
  ESF1 – ✓ ✓ Six cysteine residues Embryo surrounding micropylar endosperm cells – Regulation of suspensor cell development 

Secreted peptide hormones are translocated into the apoplastic space to reach their target cells. Because the plasma membrane is impermeant to peptides, they are recognized at the cell surface by membrane-associated receptor proteins. When the peptides bind to the apoplastic domain of the receptor, the cytoplasmic domain initiates intracellular signalling. In the case of several hormone signalling pathways, the activation of the intracellular signal results in transcriptional changes, indicating that these signals are delivered from the membrane to the nucleus and can affect transcriptional regulation. However, it is difficult to determine which molecules are working as receptors and which are working as signal transducers. In the following sections we summarize the challenges that have been encountered recently in investigations of plant peptide hormone systems, focusing on how these peptides are generated and how the mature peptides trigger downstream molecular, cellular and physiological events.

Class 1: small peptide hormones

Class 1 peptide hormones are translated as peptide precursors containing an N-terminal signal peptide, and the active domains are then excised by proteolytic processing. These active domains are generally very small (approximately 20 amino acids long), and are found in the C-terminal region of the propeptide.

CLE

In the shoot apical meristem (SAM), CLAVATA3 (CLV3), a member of the CLV3/EMBRYO SURROUNDING REGION (ESR)-RELATED (CLE) family peptides, governs the maintenance of stem cell populations [1] (Figure 2A). General features of CLE peptide precursors include the presence of an N-terminal signal peptide, and a conserved CLE domain consisting of 13 or 14 amino acid residues that is located near the C-terminus. The first arginine residue of the domain is recognized by a specific peptidase for proteolytic processing, so the active CLE peptide consists of 12 or 13 amino acids. During maturation, CLV3 peptides are known to undergo further proline hydroxylation and arabinosylation [2,3]. CLV3 is expressed in and secreted from stem cells in the SAM, and leucine-rich repeat (LRR) domain-containing receptors, namely CLAVATA1 (CLV1), CLAVATA2 (CLV2)–CORYNE (CRN)/SUPPRESSOR OF LLP1 2 (SOL2) and RECEPTOR-LIKE PROTEIN KINASE 2 (RPK2), then recognize the peptide [47]. CLV3, together with these receptors, constitutes a signalling module that is designated the CLAVATA (CLV) pathway, and it plays a role in the repression of a gene encoding a homeobox-type transcription factor (TF), WUSCHEL (WUS) [8]. Because the basic function of WUS is to promote cell proliferation in the SAM, the loss of CLV3 signalling causes the misregulation of WUS, which then leads to excessive cell proliferation in the SAM and an increase in the number of floral organs (petals, stamens and carpels). This signalling cascade also induces an increase in CLV3 expression in stem cells, thereby establishing a CLV–WUS feedback loop [8]. This feedback module helps to sustain the stem cell population in the SAM. Despite this clear feedback mechanism, the signalling modules that link the receptors and the TF are largely unknown. However, there are a few exceptions, as the mitogen-activated protein kinase (MAPK) pathway and the heterotrimeric G-protein pathway are predicted to be possible downstream components of the CLV pathway [911].

The functions of peptide hormones and their signalling components in the vegetative stage

Figure 2.
The functions of peptide hormones and their signalling components in the vegetative stage

The signalling pathways of (AD) CLE/TDIF, (E) RGF/CLEL/GLV, (F) PSY and PSK, (G) EPF/STOMAGEN and (H) RALF are shown. The peptide hormones and their receptors and signalling mediators are described in each box.

Figure 2.
The functions of peptide hormones and their signalling components in the vegetative stage

The signalling pathways of (AD) CLE/TDIF, (E) RGF/CLEL/GLV, (F) PSY and PSK, (G) EPF/STOMAGEN and (H) RALF are shown. The peptide hormones and their receptors and signalling mediators are described in each box.

Another aspect of CLE peptide function in plant development is the regulation of vascular development by tracheary element differentiation inhibitory factors (TDIFs) [12] (Figure 2B). In Arabidopsis thaliana, phloem cells express and secrete CLE41 and CLE44, which encode TDIFs, to the neighbouring procambium cells [13]. The TDIFs are recognized by a leucine-rich repeat receptor-like kinase (LRR-RLK)-type receptor, TDIF RECEPTOR (TDR), which activates the expression of WUSCHEL-RELATED HOMEOBOX 4 (WOX4), a gene that encodes a homeobox-type TF in the cambium [14]. WOX4 is capable of promoting the proliferation of cambium cells. Interestingly, and in contrast with the effect of CLV3 on WUS in the SAM, TDIF acts as a positive regulator of WOX4. Both the SAM and the vascular cells utilize similar CLE peptide–LRR receptor–WOX family TF systems. However, they stimulate different signalling pathways in a different manner. In addition to their role in the WOX4 pathway, TDIF–TDR simultaneously signals the suppression of xylem differentiation in procambium cells through glycogen synthase kinase 3 (GSK3) proteins [15]. Furthermore, BRASSINOSTEROID-INSENSITIVE 2 (BIN2) acts downstream of TIDF–TDR signalling. BIN2 directly phosphorylates AUXIN-RESPONSE FACTOR 7 (ARF7) and ARF19, and enhances auxin responses during lateral root development [16] (Figure 2C). This link suggests a role for TDIF during lateral root development.

In addition to the TDIF-class peptides, CLE45 has been identified as a root-functioning CLE peptide. The application or overexpression of CLE45 affects root growth and protophloem differentiation through a pathway that is dependent on the LRR-RLK-type receptor BARELY ANY MERISTEM 3 (BAM3) [17] (Figure 2D). This signalling module, together with the transcriptional co-regulator BREVIS RADIX (BRX) and the plasma membrane-associated protein OCTOPUS (OPS), acts during protophloem specification in the sieve element precursor cells [17,18]. The CLE peptides are biologically relevant not only in the development of the SAM and the vasculature, but also in other signalling pathways. For example, CLE6 modulates gibberellin signalling, and several CLE peptides modulate root growth under low nitrogen conditions [1921]. Furthermore, the CLE peptides are also predicted to be involved in many other biological processes, including interactions with other organisms, such as nitrogen-fixing bacteria and phytoparasitic nematodes [22,23].

RGF/CLEL/GLV

ROOT MERISTEM GROWTH FACTOR (RGF)/CLE-LIKE (CLEL)/GOLVEN (GLV) consists of 13 amino acids that are excised from a propeptide that has over 70 amino acids and contains a sulfated tyrosine residue [24]. In Arabidopsis thaliana, the RGF family peptides are encoded by nine genes, most of which are expressed in the central region of the root meristem, particularly in the quiescent centre (QC), niche cells and columella cells, and show concentration-gradient-like distributions (Figure 2E). The APETALA2 (AP2)-type TFs PLETHORA 1 (PLT1) and PLT2, which are master regulators in the root meristem, are predicted to be downstream targets of RGF/CLEL/GLV. PLT1 and PLT2 control cell proliferation, and their loss-of-function mutations greatly reduce the root meristem size. PLT1 and PLT2 display gradient-like distributions similar to those of the RGFs in the root meristem, and the mutation or application of RGF/CLEL/GLV influences the stability of the PLTs and the size of the root meristem, which suggests that RGF/CLEL/GLV controls root meristem activity through PLT1 and PLT2. Although the expression and distribution of RGF/CLEL/GLV explain their role in the root meristem, no studies on their receptors or signalling components have been reported. The identification and functional analysis of this pathway will be the next step in understanding the molecular framework of root meristem development.

Accordingly, plants that contain mutations in a gene encoding tyrosylprotein sulfotransferase (TPST), which is responsible for the sulfation of RGF/CLEL/GLV, lack undifferentiated stem cells in the root meristem, show reduced cell proliferation activity, and have a short root phenotype [24,25]. These effects are caused by the reduction of RGF/CLEL/GLV activity. Application of the mature RGF/CLEL/GLV peptide rescues the mutant phenotype, whereas application of non-sulfated RGF/CLEL/GLV is less effective. Taken together, these findings indicate that the RGF/CLEL/GLV peptides, which are sulfated by TPST, play an important role in stem cell niche maintenance in the root. However, other studies have reported that non-sulfated RGF/CLEL/GLV is also active, and it has been implicated in the control of the correct distribution of auxin [26]. The application of non-sulfated RGF/CLEL/GLV can affect root growth and gravitropic responses. The discovery of the signalling pathway will clarify the precise biological functions of the RGF/CLEL/GLV.

PSK and PSY

Phytosulfokine (PSK) is also post-translationally modified by TPST [25,27]. The A. thaliana genome harbours five PSK genes that encode precursor peptides which contain approximately 100 amino acids. PSK contains a five-amino-acid motif, YIYTQ, that is proteolytically excised, and the tyrosine residues are sulfated. PSKs are expressed in various tissues, including roots, leaves, stems, flowers and fruits (Figure 2F). This expression is consistent with the various biological effects of PSKs, including the promotion of cell proliferation, tracheary element differentiation, somatic embryogenesis, adventitious root growth and pollen germination. PSKs are recognized by both PSK receptor (PSKR) and two closely related LRR-RLK-type transmembrane receptor kinases [28]. PSK-PSKR-mediated signalling is also involved in the plant response to bacterial infection by modulating phytohormone homoeostasis in response to stress. The bacterial elicitor elf18 and/or flg22 induces the expression of PSKRs and attenuates pattern-triggered immunity [29]. This mechanism most probably contributes to the balance between biotic stress responses and effective growth.

Plant peptide containing sulfated tyrosine (PSY) is also a peptide hormone, and in A. thaliana suspension cells it is sulfated by TPST [25]. The PSY precursor is a 75-amino-acid peptide containing an 18-amino-acid active domain at the C-terminus [30]. PSY requires not only tyrosine sulfation and proteolytic processing, but also the addition of l-arabinose for full activity. Its biological effect resembles that of PSK; it also promotes cell proliferation and modulates immunity [31] (Figure 2F). Although their sizes and active domains are different, both peptide signals depend on closely related receptors.

CEP

The C-terminally encoded peptide (CEP) consists of 15 amino acids containing several hydroxylated proline residues [32]. CEP1 was first identified using a biochemical approach. Extended bioinformatics analyses then led to the discovery in the A. thaliana genome of 14 CEP genes that encode propeptides containing CEP-like domains [3234]. Interestingly, although a typical CEP propeptide contains an N-terminal signal peptide and a C-terminal CEP domain, some CEP propeptides contain multiple predicted CEP domains [34]. The expression of the CEP genes is regulated by environmental cues. In particular, nitrogen starvation induces most of the CEPs, whereas phosphate or potassium starvation does not. Recently, two LRR-RLK-type proteins, CEP RECEPTOR 1 (CEPR1) and CEPR2, were identified as CEP receptors [35]. CEPR signalling induces the expression of the nitrate transporter genes NRT2.1, NRT3.1 and NRT1.1. A well-designed split-root culture experiment showed that nitrogen-starved roots express CEPs, which are then moved to the shoots to induce nitrogen transport, establishing the systemic regulation of nitrogen homoeostasis. In addition, exogenous application or overexpression of CEPs was found to inhibit primary root growth and promote lateral root emergence. This mode of CEP action on root architecture may restrict root elongation in poor soil and promote efficient mineral uptake. Consistent with the physiological functions of the CEP peptides, the genomes of seed plants, which have modern root systems, harbour CEP homologues, whereas the latter are lacking in lower land plants [33,34]. Moreover, the expression of CEP homologues in the legume Medicago truncatula supports the formation of nodules, which are sites of nitrogen fixation [36].

IDA

The INFLORESCENCE DEFICIENT IN ABSCISSION (IDA) peptide is derived from a 77-amino-acid propeptide that contains an N-terminal signal peptide and a conserved 12-amino-acid C-terminal EPIP domain [37]. IDA is expressed in abscission zones (AZs), and facilitates the abscission of floral organs after the shedding of mature seeds (Figure 3A). Two LRR-RLK-type receptors, HAESA (HAE) and HAESA-LIKE2 (HSL2), whose expression is also detected in AZs, have been identified as IDA receptors [38]. The IDA signal triggers a MAPK cascade at the AZ that represses the expression of the KNOTTED-LIKE HOMEOBOX TF BREVIPEDICELLUS (BP)/KNOTTED-LIKE FROM ARABIDOPSIS THALIANA1 (KNAT1), through which IDA influences the expression of KNAT2 and KNAT6 [39]. Moreover, the IDA-HAE and IDA-HSL2 modules also function during lateral root emergence [40]. Prominent IDA promoter activity has been observed in the cells surrounding the lateral roots. HAE and HSL2 are also expressed during lateral root emergence, but their expression does not completely overlap. The downstream consequence of IDA signalling is the remodelling of the cell wall. During both floral organ abscission and lateral root emergence the plant requires multistep enzymatic reactions that promote cell wall loosening by expansins and xyloglucan endotransglucosylase/hydrolases, followed by cell wall degradation by polygalacturonases. Several genes that encode such enzymes are downstream of IDA signalling [40].

The functions of peptide hormones and their signalling components in flowers

Figure 3.
The functions of peptide hormones and their signalling components in flowers

The signalling pathways of (A) IDA, (B) SCR, (C) LURE, (D) RALF and (E) ESF are shown. The peptide hormones and their receptors and signalling mediators are described in each box.

Figure 3.
The functions of peptide hormones and their signalling components in flowers

The signalling pathways of (A) IDA, (B) SCR, (C) LURE, (D) RALF and (E) ESF are shown. The peptide hormones and their receptors and signalling mediators are described in each box.

Class 2: peptide hormones with disulfide bonds

Class 2 peptide hormones are classified as defensin-like cysteine-rich peptides. They contain several cysteine residues that form disulfide bonds. Because their stereoscopic structure is crucial for their activity, these peptides are heat-sensitive. The most remarkable feature of this class of peptides is that they have highly variable sequences, but their core structure is conserved, which may be advantageous for their role.

SCR/SP11

Self-incompatibility is the ability to inhibit self-fertilization, and it is frequently observed in plants, particularly those that are hermaphrodite. Self-incompatibility is an important mechanism for promoting cross-fertilization and producing genetic variation. S-LOCUS CYSTEINE-RICH PROTEIN (SCR)/SP11 has been specifically studied in Brassica species, and has been reported to be a male determinant of sporophytic self-incompatibility in the Brassicaceae [41] (Figure 3B). This small peptide, which belongs to the defensin-like protein family, contains an N-terminal signal peptide. It is secreted from pollen cells and then coats the pollen's surface [42]. SCR peptides are recognized by the transmembrane receptor kinase S-locus receptor kinase (SRK) and by S-locus glycoprotein (SLG), both of which are expressed in stigma cells [4345]. Self-incompatible plants have developed several haplotypes to distinguish themselves from others. When the haplotypes of the pollen and stigma are identical, a cytoplasmic kinase, M-locus protein kinase (MLPK), triggers cytoplasmic signalling [46]. Downstream molecular event(s) somehow render the pollen and stigma self-incompatible and prevent the pollen from penetrating the stigma. By contrast, although it belongs to the Brassicaceae, the model plant A. thaliana is self-compatible. However, this is explained by the fact that it contains mutations in the S-locus that make the self-incompatibility system non-functional [47].

LURE

Two defensin-like polypeptides are secreted from synergid cells in Torenia fournieri and function as pollen tube attractants [48]. These peptides, known as LUREs, contain six cysteine residues that form disulfide bonds which are essential for their activity (Figure 3C). The LURE peptides are proteolytically processed, secreted and transported to the micropylar surface of the filiform apparatus. Pollen tubes somehow sense the LUREs, grow towards them and enter the ovule to complete fertilization. Because LURE peptide sequences are thought to be highly species-specific, pollen tube attraction cannot be mediated by LUREs from other species. In fact, LUREs from A. thaliana are completely different from those from T. fournieri, except for the six conserved cysteine residues [49]. Defensin-like genes are thought to evolve rapidly. The species specificity of the LURE peptides may help to establish the species specificity of pollen attraction.

Class 3: processed peptide hormones with disulfide bonds

Class 3 peptide hormones require both proteolytic processing and disulfide bond formation via their cysteine residues. In contrast with class 2 defensin-like peptides, the primary amino acid sequences of class 3 peptides are relatively conserved.

EPF/STOMAGEN

Land plants have established highly organized gas-exchange systems that include stomata, which are pores of adjustable size in the leaf epidermal cell layer. To form stomata, plants have developed well-defined multistep differentiation pathways. Guard cells are derived from undifferentiated epidermal protoderm cells. Most epidermal cells differentiate into jigsaw-puzzle-piece-shaped pavement cells, whereas a subset of the protoderm cells differentiate into other cell types, including meristemoid mother cells (MMCs). The MMC sequentially divides and differentiates to generate the stomatal lineage ground cell (SLGC) and the meristemoid. Finally, the meristemoids differentiate into guard mother cells (GMCs), and the GMCs divide symmetrically to generate guard cells (GCs).

Guard cell density is genetically determined, although plants sometimes change this developmental programme in response to environmental cues. EPIDERMAL PATTERNING FACTOR 1 (EPF1) and EPF2 are negative regulators of guard cell development in leaves [50,51] (Figure 2G). The active forms of these peptides originate from a C-terminal 45-amino-acid peptide containing six cysteine residues that form disulfide bonds to create the EPF core structure. EPF2 is expressed in the MMC and meristemoid to prevent the surrounding cells from entering the guard cell lineage. EPF1 is expressed in late meristemoids and GMCs, and negatively regulates the late differentiation steps. Therefore loss-of-function mutations in EPF1 and EPF2 cause cells in the guard cell lineage to cluster on the leaf epidermis. The LRR-RLK-type receptor kinases ERECTA (ER), ERECTA-LIKE1 (ERL1) and ERL2, as well as the LRR protein TOO MANY MOUTHS (TMM), have been shown to be receptors for the EPFs [50,52]. The downstream effects of these LRR-RLK receptors are predicted to influence the basic helix–loop–helix (bHLH) family of TFs, including SPEECHLESS (SPCH), MUTE and FAMA, which regulate developmental processes via the MAPK cascade composed of YODA (MAPK kinase kinase or MAPKKK), MKK4 and MKK5 (MAPK kinases or MAPKKs), and MPK3 and MPK6 (MAPKs) [53]. Conversely, STOMAGEN/EPFL9 (hereafter referred to as STOMAGEN) has been identified as a positive regulator of stomatal density [54] (Figure 2G). Although the sequence of STOMAGEN is similar to those of other EPF family members, it has the opposite effect, as the overexpression or application of STOMAGEN leads to clustered stomata on the leaves. Interestingly, STOMAGEN is expressed in photosynthesizing mesophyll cells and moves to the epidermis to regulate stomatal density, which suggests that there is an interlayer control of stomatal density, possibly to ensure the fine-tuning of gas-exchange efficiency. On the basis of genetic analyses, the effect of STOMAGEN requires EPF2, TMM and SPCH, which suggests that STOMAGEN and the EPFs act antagonistically on the receptors. Recently, a novel CO2-induced extracellular protease, CO2-RESPONSE SECRETED PROTEASE (CRSP), was identified as a mediator of CO2-controlled stomatal development. CRSP cleaves the EPF2 propeptide and represses stomatal development. [55]

RALF

Tobacco RAPID ALKALINIZATION FACTOR (RALF) consists of a 115-amino-acid peptide containing an N-terminal signal peptide [56]. The active domain of RALF is encoded at the C-terminus and is composed of 49 amino acids, including four cysteine residues which form disulfide bonds that are essential for the activity of RALF. RALF peptides induce cell acidification and expansion [57]. When plants were grown on medium containing the RALF peptide, an increase in cytoplasmic calcium concentration and in the pH of the medium was observed, as well as the inhibition of root growth (Figure 2H). Furthermore, RALF peptides inhibit cell elongation in pollen tubes, microcalli and hypocotyls [57] (Figure 3D). Recently, a plasma membrane-localized receptor-like kinase, FERONIA (FER), was identified as a receptor for RALF [58]. RALF–FER binding influences the phosphorylation state of various proteins. Plasma membrane-localized H+-ATPase 2 (AHA2), which secretes protons into the apoplast, is one of the proteins that FER targets in response to RALF application. Consistent with the effect of exogenous RALF application, the phosphorylation of AHA2 decreases its function and causes apoplastic alkalinization, which suggests that RALF negatively regulates AHA2 function through the FER receptor.

ESF1

The initial stage of plant development is the establishment of the embryo and the supporting suspensor cells in the ovules. The central cells of non-fertilized ovules and, in the later stages, the embryo and the surrounding micropylar endosperm cells, express and secrete a cysteine-rich peptide designated EMBRYO SURROUNDING FACTOR 1 (ESF1) [59] (Figure 3E). The active domain of ESF1 consists of 68 amino acid residues, including six cysteine residues that form disulfide bonds. Genetic evidence suggests that ESF1 activates a MAPK cascade via the YODA MAPKKK to facilitate the development of the suspensor cells and the correct distribution of auxin in the early stages of embryo development. Although ESF1 is required for the formation of the suspensor cells, the specificity of its expression varies, which suggests a non-cell-autonomous function. Although specific receptors for ESF1 have yet to be identified, they probably function as an interface for intercellular signals, and may provide evidence of the importance of such cell-to-cell communication in early embryogenesis.

Conclusion and perspective

Peptide hormones are employed in multiple aspects of the plant life cycle (Figures 2 and 3). In addition to the peptides that have been described in this chapter, several other secreted peptides that are considered to be phytohormones have been identified. For example, SYSTEMIN was isolated from tomato leaves and was the first hormone that was demonstrated to be capable of activating defence responses against wounding [60]. Biochemical approaches have shown that SYSTEMIN is recognized by an LRR-RLK-type transmembrane receptor, and that its signalling is mediated by MAPK cascades [61]. ROTUNDIFOLIA FOUR-LIKE/DEVIL (RTFL/DVL) regulates cell division polarity. However, its mode of action is still being investigated [62,63]. EGG CELL1 (EC1) is a cysteine-rich peptide that accumulates in and is secreted from the egg cell to facilitate sperm cell activation during double fertilization. Although the conserved two signature motifs that contain six cysteine residues suggest a requirement for a disulfide bond for the functioning of EC1, investigations of the precise structure and signalling pathway will be needed [64]. Most of the known peptide hormones have been identified using genetic and biochemical approaches. For example, CLV3 and IDA were first isolated on the basis of mutant phenotypes, and SYSTEMIN, CEP and RALF were isolated from leaves using biochemical purification techniques. In addition, recent advances in bioinformatics have aided the discovery of small peptides, such as RGF, EPF and CEP. However, it would not be surprising if additional peptide hormones are discovered in the future. The application of next-generation sequencing techniques will be a powerful tool for identifying novel small open reading frames that contain candidate genes encoding small peptides (as has, for example, been described by Hanada et al. [65]).

The most important steps involved in understanding peptide hormone signalling are the identification of receptor proteins and downstream signalling molecules. Almost all peptide hormones are thought to be secreted into the apoplast and recognized by transmembrane receptors. Importantly, most of the previously identified peptide hormone receptors are receptor kinases, and specifically CLE/TDIF, PSK/PSY1, IDA, EPF/STOMAGEN and SYSTEMIN require LRR-RLK-type receptors. Moreover, the MAPK cascade is thought to function downstream of these peptide hormones, in a similar way to that in which the YODA-mediated MAPK signalling module functions downstream of ESF1. The plant genome is known to encode a huge number of receptor kinases and MAPK components. Therefore the specific molecules that are responsible for linking these pathways have yet to be identified. In the CLV3 signalling pathway, CLV1 can bind to the kinase-associated protein phosphatase (KAPP), and a Rho GTPase-related protein and eukaryotically conserved heterotrimeric G-proteins have been identified as signalling mediators in the CLV pathway in maize and Arabidopsis thaliana [10,11]. It was recently reported that a receptor-like cytoplasmic kinase (RLCK) mediates signals from an LRR-RLK to a MAPK in response to disease [66]. Numerous proteins with unidentified functions belong to the RLCK protein family, which suggests that the RLCKs have pleiotropic functions. These findings raise the interesting possibility that the RCLKs act as signalling mediators in peptide hormone signalling. Nevertheless, elucidation of the way in which signals that are recognized at the membrane are transmitted into cells is the next major area of study in this field.

Summary

  • Peptide hormones are employed in multiple aspects of the plant life cycle.

  • Class 1 peptide hormones are very small peptides that are proteolytically processed to excise their active domain.

  • Class 2 defensin-like cysteine-rich peptide hormones require disulfide bonds for their stereoscopic structure.

  • Class 3 peptide hormones require both proteolytic processing and disulfide bond formation.

  • Most plant peptide hormone receptors are plasma-membrane-localized kinases.

  • The binding of peptide hormones to their receptors triggers intracellular signalling.

  • The identification of peptide hormone receptors and signalling components may improve our understanding of peptide hormone signalling.

References

References
1.
Clark
 
S.E.
Running
 
M.P.
Meyerowitz
 
E.M.
 
CLAVATA3 is a specific regulator of shoot and floral meristem development affecting the same processes as CLAVATA1
Development
1995
, vol. 
121
 (pg. 
2057
-
2067
)
2.
Kondo
 
T.
Sawa
 
S.
Kinoshita
 
A.
Mizuno
 
S.
Kakimoto
 
T.
Fukuda
 
H.
Sakagami
 
Y.
 
A plant peptide encoded by CLV3 identified by in situ MALDI-TOF MS analysis
Science
2006
, vol. 
313
 (pg. 
845
-
848
)
3.
Ohyama
 
K.
Shinohara
 
H.
Ogawa-Ohnishi
 
M.
Matsubayashi
 
Y.
 
A glycopeptide regulating stem cell fate in Arabidopsis thaliana
Nat. Chem. Biol.
2009
, vol. 
5
 (pg. 
578
-
580
)
4.
Ogawa
 
M.
Shinohara
 
H.
Sakagami
 
Y.
Matsubayashi
 
Y.
 
Arabidopsis CLV3 peptide directly binds CLV1 ectodomain
Science
2008
, vol. 
319, 294
 
5.
Kinoshita
 
A.
Betsuyaku
 
S.
Osakabe
 
Y.
Mizuno
 
S.
Nagawa
 
S.
Stahl
 
Y.
Simon
 
R.
Yamaguchi-Shinozaki
 
K.
Fukuda
 
H.
Sawa
 
S.
 
RPK2 is an essential receptor-like kinase that transmits the CLV3 signal in Arabidopsis
Development
2010
, vol. 
137
 (pg. 
3911
-
3920
)
6.
Miwa
 
H.
Betsuyaku
 
S.
Iwamoto
 
K.
Kinoshita
 
A.
Fukuda
 
H.
Sawa
 
S.
 
The receptor-like kinase SOL2 mediates CLE signaling in Arabidopsis
Plant Cell Physiol.
2008
, vol. 
49
 (pg. 
1752
-
1757
)
7.
Muller
 
R.
Bleckmann
 
A.
Simon
 
R.
 
The receptor kinase CORYNE of Arabidopsis transmits the stem cell-limiting signal CLAVATA3 independently of CLAVATA1
Plant Cell
2008
, vol. 
20
 (pg. 
934
-
946
)
8.
Schoof
 
H.
Lenhard
 
M.
Haecker
 
A.
Mayer
 
K.F.
Jurgens
 
G.
Laux
 
T.
 
The stem cell population of Arabidopsis shoot meristems is maintained by a regulatory loop between the CLAVATA and WUSCHEL genes
Cell
2000
, vol. 
100
 (pg. 
635
-
644
)
9.
Betsuyaku
 
S.
Takahashi
 
F.
Kinoshita
 
A.
Miwa
 
H.
Shinozaki
 
K.
Fukuda
 
H.
Sawa
 
S.
 
Mitogen-activated protein kinase regulated by the CLAVATA receptors contributes to shoot apical meristem homeostasis
Plant Cell Physiol.
2011
, vol. 
52
 (pg. 
14
-
29
)
10.
Ishida
 
T.
Tabata
 
R.
Yamada
 
M.
Aida
 
M.
Mitsumasu
 
K.
Fujiwara
 
M.
Yamaguchi
 
K.
Shigenobu
 
S.
Higuchi
 
M.
Tsuji
 
H.
, et al 
Heterotrimeric G proteins control stem cell proliferation through CLAVATA signaling in Arabidopsis
EMBO Rep.
2014
, vol. 
15
 (pg. 
1202
-
1209
)
11.
Bommert
 
P.
Je
 
B.I.
Goldshmidt
 
A.
Jackson
 
D.
 
The maize Gα gene COMPACT PLANT2 functions in CLAVATA signalling to control shoot meristem size
Nature
2013
, vol. 
502
 (pg. 
555
-
558
)
12.
Ito
 
Y.
Nakanomyo
 
I.
Motose
 
H.
Iwamoto
 
K.
Sawa
 
S.
Dohmae
 
N.
Fukuda
 
H.
 
Dodeca-CLE peptides as suppressors of plant stem cell differentiation
Science
2006
, vol. 
313
 (pg. 
842
-
845
)
13.
Hirakawa
 
Y.
Shinohara
 
H.
Kondo
 
Y.
Inoue
 
A.
Nakanomyo
 
I.
Ogawa
 
M.
Sawa
 
S.
Ohashi-Ito
 
K.
Matsubayashi
 
Y.
Fukuda
 
H.
 
Non-cell-autonomous control of vascular stem cell fate by a CLE peptide/receptor system
Proc. Natl. Acad. Sci. U.S.A.
2008
, vol. 
105
 (pg. 
15208
-
15213
)
14.
Hirakawa
 
Y.
Kondo
 
Y.
Fukuda
 
H.
 
TDIF peptide signaling regulates vascular stem cell proliferation via the WOX4 homeobox gene in Arabidopsis
Plant Cell
2010
, vol. 
22
 (pg. 
2618
-
2629
)
15.
Kondo
 
Y.
Ito
 
T.
Nakagami
 
H.
Hirakawa
 
Y.
Saito
 
M.
Tamaki
 
T.
Shirasu
 
K.
Fukuda
 
H.
 
Plant GSK3 proteins regulate xylem cell differentiation downstream of TDIF–TDR signalling
Nat. Commun.
2014
, vol. 
5
 pg. 
3504
 
16.
Cho
 
H.
Ryu
 
H.
Rho
 
S.
Hill
 
K.
Smith
 
S.
Audenaert
 
D.
Park
 
J.
Han
 
S.
Beeckman
 
T.
Bennett
 
M.J.
, et al 
A secreted peptide acts on BIN2-mediated phosphorylation of ARFs to potentiate auxin response during lateral root development
Nat. Cell Biol.
2014
, vol. 
16
 (pg. 
66
-
76
)
17.
Depuydt
 
S.
Rodriguez-Villalon
 
A.
Santuari
 
L.
Wyser-Rmili
 
C.
Ragni
 
L.
Hardtke
 
C.S.
 
Suppression of Arabidopsis protophloem differentiation and root meristem growth by CLE45 requires the receptor-like kinase BAM3
Proc. Natl. Acad. Sci. U.S.A.
2013
, vol. 
110
 (pg. 
7074
-
7079
)
18.
Rodriguez-Villalon
 
A.
Gujas
 
B.
Kang
 
Y.H.
Breda
 
A.S.
Cattaneo
 
P.
Depuydt
 
S.
Hardtke
 
C.S.
 
Molecular genetic framework for protophloem formation
Proc. Natl. Acad. Sci. U.S.A.
2014
, vol. 
111
 (pg. 
11551
-
11556
)
19.
Endo
 
S.
Shinohara
 
H.
Matsubayashi
 
Y.
Fukuda
 
H.
 
A novel pollen-pistil interaction conferring high-temperature tolerance during reproduction via CLE45 signaling
Curr. Biol.
2013
, vol. 
23
 (pg. 
1670
-
1676
)
20.
Bidadi
 
H.
Matsuoka
 
K.
Sage-Ono
 
K.
Fukushima
 
J.
Pitaksaringkarn
 
W.
Asahina
 
M.
Yamaguchi
 
S.
Sawa
 
S.
Fukuda
 
H.
Matsubayashi
 
Y.
, et al 
CLE6 expression recovers gibberellin deficiency to promote shoot growth in Arabidopsis
Plant J.
2014
, vol. 
78
 (pg. 
241
-
252
)
21.
Araya
 
T.
Miyamoto
 
M.
Wibowo
 
J.
Suzuki
 
A.
Kojima
 
S.
Tsuchiya
 
Y.N.
Sawa
 
S.
Fukuda
 
H.
von Wirén
 
N.
Takahashi
 
H.
 
CLE-CLAVATA1 peptide-receptor signaling module regulates the expansion of plant root systems in a nitrogen-dependent manner
Proc. Natl. Acad. Sci. U.S.A.
2014
, vol. 
111
 (pg. 
2029
-
2034
)
22.
Wang
 
J.
Replogle
 
A.
Hussey
 
R.
Baum
 
T.
Wang
 
X.
Davis
 
E.L.
Mitchum
 
M.G.
 
Identification of potential host plant mimics of CLAVATA3/ESR (CLE)–like peptides from the plant-parasitic nematode Heterodera schachtii
Mol. Plant Pathol.
2011
, vol. 
12
 (pg. 
177
-
186
)
23.
Okamoto
 
S.
Ohnishi
 
E.
Sato
 
S.
Takahashi
 
H.
Nakazono
 
M.
Tabata
 
S.
Kawaguchi
 
M.
 
Nod factor/nitrate-induced CLE genes that drive HAR1-mediated systemic regulation of nodulation
Plant Cell Physiol.
2009
, vol. 
50
 (pg. 
67
-
77
)
24.
Matsuzaki
 
Y.
Ogawa-Ohnishi
 
M.
Mori
 
A.
Matsubayashi
 
Y.
 
Secreted peptide signals required for maintenance of root stem cell niche in Arabidopsis
Science
2010
, vol. 
329
 (pg. 
1065
-
1067
)
25.
Komori
 
R.
Amano
 
Y.
Ogawa-Ohnishi
 
M.
Matsubayashi
 
Y.
 
Identification of tyrosylprotein sulfotransferase in Arabidopsis
Proc. Natl. Acad. Sci. U.S.A.
2009
, vol. 
106
 (pg. 
15067
-
15072
)
26.
Whitford
 
R.
Fernandez
 
A.
Tejos
 
R.
Cuéllar Pérez
 
A.
Kleine-Vehn
 
J.
Vanneste
 
S.
Drozdzecki
 
A.
Leitner
 
J.
Abas
 
L.
Aerts
 
M.
, et al 
GOLVEN secretory peptides regulate auxin carrier turnover during plant gravitropic responses
Dev. Cell
2012
, vol. 
22
 (pg. 
678
-
685
)
27.
Matsubayashi
 
Y.
Sakagami
 
Y.
 
Phytosulfokine, sulfated peptides that induce the proliferation of single mesophyll cells of Asparagus officinalis L
Proc. Natl. Acad. Sci. U.S.A.
1996
, vol. 
93
 (pg. 
7623
-
7627
)
28.
Matsubayashi
 
Y.
Ogawa
 
M.
Morita
 
A.
Sakagami
 
Y.
 
An LRR receptor kinase involved in perception of a peptide plant hormone, phytosulfokine
Science
2002
, vol. 
296
 (pg. 
1470
-
1472
)
29.
Igarashi
 
D.
Tsuda
 
K.
Katagiri
 
F.
 
The peptide growth factor, phytosulfokine, attenuates pattern-triggered immunity
Plant J.
2012
, vol. 
71
 (pg. 
194
-
204
)
30.
Amano
 
Y.
Tsubouchi
 
H.
Shinohara
 
H.
Ogawa
 
M.
Matsubayashi
 
Y.
 
Tyrosine-sulfated glycopeptide involved in cellular proliferation and expansion in Arabidopsis
Proc. Natl. Acad. Sci. U.S.A.
2007
, vol. 
104
 (pg. 
18333
-
18338
)
31.
Mosher
 
S.
Seybold
 
H.
Rodriguez
 
P.
Stahl
 
M.
Davies
 
K.A.
Dayaratne
 
S.
Morillo
 
S.A.
Wierzba
 
M.
Favery
 
B.
Keller
 
H.
, et al 
The tyrosine-sulfated peptide receptors PSKR1 and PSY1R modify the immunity of Arabidopsis to biotrophic and necrotrophic pathogens in an antagonistic manner
Plant J.
2013
, vol. 
73
 (pg. 
469
-
482
)
32.
Ohyama
 
K.
Ogawa
 
M.
Matsubayashi
 
Y.
 
Identification of a biologically active, small, secreted peptide in Arabidopsis by in silico gene screening, followed by LC-MS-based structure analysis
Plant J.
2008
, vol. 
55
 (pg. 
152
-
160
)
33.
Delay
 
C.
Imin
 
N.
Djordjevic
 
M.A.
 
CEP genes regulate root and shoot development in response to environmental cues and are specific to seed plants
J. Exp. Bot.
2013
, vol. 
64
 (pg. 
5383
-
5394
)
34.
Roberts
 
I.
Smith
 
S.
De Rybel
 
B.
Van Den Broeke
 
J.
Smet
 
W.
De Cokere
 
S.
Mispelaere
 
M.
De Smet
 
I.
Beeckman
 
T.
 
The CEP family in land plants: evolutionary analyses, expression studies, and role in Arabidopsis shoot development
J. Exp. Bot.
2013
, vol. 
64
 (pg. 
5371
-
5381
)
35.
Tabata
 
R.
Sumida
 
K.
Yoshii
 
T.
Ohyama
 
K.
Shinohara
 
H.
Matsubayashi
 
Y.
 
Perception of root-derived peptides by shoot LRR-RKs mediates systemic N-demand signaling
Science
2014
, vol. 
346
 (pg. 
343
-
346
)
36.
Imin
 
N.
Mohd-Radzman
 
N.A.
Ogilvie
 
H.A.
Djordjevic
 
M.A.
 
The peptide-encoding CEP1 gene modulates lateral root and nodule numbers in Medicago truncatula
J. Exp. Bot.
2013
, vol. 
64
 (pg. 
5395
-
5409
)
37.
Butenko
 
M.A.
Patterson
 
S.E.
Grini
 
P.E.
Stenvik
 
G.E.
Amundsen
 
S.S.
Mandal
 
A.
Aalen
 
R.B.
 
Inflorescence deficient in abscission controls floral organ abscission in Arabidopsis and identifies a novel family of putative ligands in plants
Plant Cell
2003
, vol. 
15
 (pg. 
2296
-
2307
)
38.
Stenvik
 
G.E.
Tandstad
 
N.M.
Guo
 
Y.
Shi
 
C.L.
Kristiansen
 
W.
Holmgren
 
A.
Clark
 
S.E.
Aalen
 
R.B.
Butenko
 
M.A.
 
The EPIP peptide of INFLORESCENCE DEFICIENT IN ABSCISSION is sufficient to induce abscission in Arabidopsis through the receptor-like kinases HAESA and HAESA-LIKE2
Plant Cell
2008
, vol. 
20
 (pg. 
1805
-
1817
)
39.
Shi
 
C.L.
Stenvik
 
G.E.
Vie
 
A.K.
Bones
 
A.M.
Pautot
 
V.
Proveniers
 
M.
Aalen
 
R.B.
Butenko
 
M.A.
 
Arabidopsis class I KNOTTED-like homeobox proteins act downstream in the IDA-HAE/HSL2 floral abscission signaling pathway
Plant Cell
2011
, vol. 
23
 (pg. 
2553
-
2567
)
40.
Kumpf
 
R.P.
Shi
 
C.L.
Larrieu
 
A.
Sto
 
I.M.
Butenko
 
M.A.
Peret
 
B.
Riiser
 
E.S.
Bennett
 
M.J.
Aalen
 
R.B.
 
Floral organ abscission peptide IDA and its HAE/HSL2 receptors control cell separation during lateral root emergence
Proc. Natl. Acad. Sci. U.S.A.
2013
, vol. 
110
 (pg. 
5235
-
5240
)
41.
Schopfer
 
C.R.
Nasrallah
 
M.E.
Nasrallah
 
J.B.
 
The male determinant of self-incompatibility in Brassica
Science
1999
, vol. 
286
 (pg. 
1697
-
1700
)
42.
Takayama
 
S.
Shiba
 
H.
Iwano
 
M.
Shimosato
 
H.
Che
 
F.-S.
Kai
 
N.
Watanabe
 
M.
Suzuki
 
G.
Hinata
 
K.
Isogai
 
A.
 
The pollen determinant of self-incompatibility in Brassica campestris
Proc. Natl. Acad. Sci. U.S.A.
2000
, vol. 
97
 (pg. 
1920
-
1925
)
43.
Stein
 
J.C.
Howlett
 
B.
Boyes
 
D.C.
Nasrallah
 
M.E.
Nasrallah
 
J.B.
 
Molecular cloning of a putative receptor protein kinase gene encoded at the self-incompatibility locus of Brassica oleracea
Proc. Natl. Acad. Sci. U.S.A
1991
, vol. 
88
 (pg. 
8816
-
8820
)
44.
Takayama
 
S.
Shimosato
 
H.
Shiba
 
H.
Funato
 
M.
Che
 
F.-S.
Watanabe
 
M.
Iwano
 
M.
Isogai
 
A.
 
Direct ligand-receptor complex interaction controls Brassica self–incompatibility
Nature
2001
, vol. 
413
 (pg. 
534
-
538
)
45.
Takasaki
 
T.
Hatakeyama
 
K.
Suzuki
 
G.
Watanabe
 
M.
Isogai
 
A.
Hinata
 
K.
 
The S receptor kinase determines self-incompatibility in Brassica stigma
Nature
2000
, vol. 
403
 (pg. 
913
-
916
)
46.
Kakita
 
M.
Murase
 
K.
Iwano
 
M.
Matsumoto
 
T.
Watanabe
 
M.
Shiba
 
H.
Isogai
 
A.
Takayama
 
S.
 
Two distinct forms of M-locus protein kinase localize to the plasma membrane and interact directly with S-locus receptor kinase to transduce self-incompatibility signaling in Brassica rapa
Plant Cell
2007
, vol. 
19
 (pg. 
3961
-
3973
)
47.
Kusaba
 
M.
Dwyer
 
K.
Hendershot
 
J.
Vrebalov
 
J.
Nasrallah
 
J.B.
Nasrallah
 
M.E.
 
Self-incompatibility in the genus Arabidopsis: characterization of the S locus in the outcrossing A. lyrata and its autogamous relative A. thaliana
Plant Cell
2001
, vol. 
13
 (pg. 
627
-
643
)
48.
Okuda
 
S.
Tsutsui
 
H.
Shiina
 
K.
Sprunck
 
S.
Takeuchi
 
H.
Yui
 
R.
Kasahara
 
R.D.
Hamamura
 
Y.
Mizukami
 
A.
Susaki
 
D.
, et al 
Defensin-like polypeptide LUREs are pollen tube attractants secreted from synergid cells
Nature
2009
, vol. 
458
 (pg. 
357
-
361
)
49.
Takeuchi
 
H.
Higashiyama
 
T.
 
A species-specific cluster of defensin-like genes encodes diffusible pollen tube attractants in Arabidopsis
PLoS Biol.
2012
, vol. 
10
 pg. 
e1001449
 
50.
Hara
 
K.
Kajita
 
R.
Torii
 
K.U.
Bergmann
 
D.C.
Kakimoto
 
T.
 
The secretory peptide gene EPF1 enforces the stomatal one-cell-spacing rule
Genes Dev.
2007
, vol. 
21
 (pg. 
1720
-
1725
)
51.
Hunt
 
L.
Gray
 
J.E.
 
The signaling peptide EPF2 controls asymmetric cell divisions during stomatal development
Curr. Biol.
2009
, vol. 
19
 (pg. 
864
-
869
)
52.
Lee
 
J.S.
Kuroha
 
T.
Hnilova
 
M.
Khatayevich
 
D.
Kanaoka
 
M.M.
McAbee
 
J.M.
Sarikaya
 
M.
Tamerler
 
C.
Torii
 
K.U.
 
Direct interaction of ligand–receptor pairs specifying stomatal patterning
Genes Dev.
2012
, vol. 
26
 (pg. 
126
-
136
)
53.
Lau
 
O.S.
Bergmann
 
D.C.
 
Stomatal development: a plant's perspective on cell polarity, cell fate transitions and intercellular communication
Development
2012
, vol. 
139
 (pg. 
3683
-
3692
)
54.
Sugano
 
S.S.
Shimada
 
T.
Imai
 
Y.
Okawa
 
K.
Tamai
 
A.
Mori
 
M.
Hara-Nishimura
 
I.
 
Stomagen positively regulates stomatal density in Arabidopsis
Nature
2010
, vol. 
463
 (pg. 
241
-
244
)
55.
Engineer
 
C.B.
Ghassemian
 
M.
Anderson
 
J.C.
Peck
 
S.C.
Hu
 
H.
Schroeder
 
J.I.
 
Carbonic anhydrases, EPF2 and a novel protease mediate CO2 control of stomatal development
Nature
2014
, vol. 
513
 (pg. 
246
-
250
)
56.
Pearce
 
G.
Moura
 
D.S.
Stratmann
 
J.
Ryan
 
C.A.
 
RALF, a 5-kDa ubiquitous polypeptide in plants, arrests root growth and development
Proc. Natl. Acad. Sci. U.S.A.
2001
, vol. 
98
 (pg. 
12843
-
12847
)
57.
Murphy
 
E.
De Smet
 
I.
 
Understanding the RALF family: a tale of many species
Trends Plant Sci.
2014
, vol. 
19
 (pg. 
664
-
671
)
58.
Haruta
 
M.
Sabat
 
G.
Stecker
 
K.
Minkoff
 
B.B.
Sussman
 
M.R.
 
A peptide hormone and its receptor protein kinase regulate plant cell expansion
Science
2014
, vol. 
343
 (pg. 
408
-
411
)
59.
Costa
 
L.M.
Marshall
 
E.
Tesfaye
 
M.
Silverstein
 
K.A.T.
Mori
 
M.
Umetsu
 
Y.
Otterbach
 
S.L.
Papareddy
 
R.
Dickinson
 
H.G.
Boutiller
 
K.
, et al 
Central cell-derived peptides regulate early embryo patterning in flowering plants
Science
2014
, vol. 
344
 (pg. 
168
-
172
)
60.
McGurl
 
B.
Pearce
 
G.
Orozco-Cardenas
 
M.
Ryan
 
C.A.
 
Structure, expression, and antisense inhibition of the systemin precursor gene
Science
1992
, vol. 
255
 (pg. 
1570
-
1573
)
61.
Scheer
 
J.M.
Ryan
 
C.A.
 
The systemin receptor SR160 from Lycopersicon peruvianum is a member of the LRR receptor kinase family
Proc. Natl. Acad. Sci. U.S.A.
2002
, vol. 
99
 (pg. 
9585
-
9590
)
62.
Narita
 
N.N.
Moore
 
S.
Horiguchi
 
G.
Kubo
 
M.
Demura
 
T.
Fukuda
 
H.
Goodrich
 
J.
Tsukaya
 
H.
 
Overexpression of a novel small peptide ROTUNDIFOLIA4 decreases cell proliferation and alters leaf shape in Arabidopsis thaliana
Plant J.
2004
, vol. 
38
 (pg. 
699
-
713
)
63.
Wen
 
J.
Lease
 
K.A.
Walker
 
J.C.
 
DVL, a novel class of small polypeptides: overexpression alters Arabidopsis development
Plant J.
2004
, vol. 
37
 (pg. 
668
-
677
)
64.
Sprunck
 
S.
Rademacher
 
S.
Vogler
 
F.
Gheyselinck
 
J.
Grossniklaus
 
U.
Dresselhaus
 
T.
 
Egg cell-secreted EC1 triggers sperm cell activation during double fertilization
Science
2012
, vol. 
338
 (pg. 
1093
-
1097
)
65.
Hanada
 
K.
Higuchi-Takeuchi
 
M.
Okamoto
 
M.
Yoshizumi
 
T.
Shimizu
 
M.
Nakaminami
 
K.
Nishi
 
R.
Ohashi
 
C.
Iida
 
K.
Tanaka
 
M.
, et al 
Small open reading frames associated with morphogenesis are hidden in plant genomes
Proc. Natl. Acad. Sci. U.S.A.
2013
, vol. 
110
 (pg. 
2395
-
2400
)
66.
Yamaguchi
 
K.
Yamada
 
K.
Ishikawa
 
K.
Yoshimura
 
S.
Hayashi
 
N.
Uchihashi
 
K.
Ishihama
 
N.
Kishi-Kaboshi
 
M.
Takahashi
 
A.
Tsuge
 
S.
, et al 
A receptor-like cytoplasmic kinase targeted by a plant pathogen effector is directly phosphorylated by the chitin receptor and mediates rice immunity
Cell Host Microbe
2013
, vol. 
13
 (pg. 
347
-
357
)