Phosphatidylserine (PtdSer) is synthesized in the endoplasmic reticulum and its subdomains associated with the mitochondria [MAM (mitochondria-associated membrane)] and subsequently transported to the loci of the PtdSer decarboxylases, Pds1p (phosphatidylserine decarboxylase 1 encoded by the PSD1 gene that complements psd1 mutations) in the mitochondria, and Psd2p (PtdSer decarboxylase 2 encoded by the PSD2 gene that complements psd2 mutations) in the Golgi. Decarboxylation of PtdSer to PtdEtn (phosphatidylethanolamine) can be used as a biochemical indicator of transport to these organelles, which is regulated by specific lipid and protein motifs. PtdSer transport to mitochondria is controlled by ubiquitination via the action of the ubiquitin ligase subunit Met30p (a ubiquitin ligase subunit encoded by the MET30 gene that complements the met30 mutation affecting methionine biosynthesis). Mutant strains with lesions in the MET30 gene are defective in PtdSer transport and show altered ubiquitination of specific target proteins, such as the transcription factor Met4p (a transcription factor encoded by the MET4 gene that complements the met4 mutation affecting methionine biosynthesis). Mutations to MET30 cause defects in both the MAM as a donor of PtdSer, and the mitochondria as an acceptor of PtdSer in the transport reaction. PtdSer transport to the locus of Psd2p is controlled by specific protein and lipid motifs. The C2 (Ca2+ and phospholipid-binding sequence) domain of Psd2p, and the lipid-binding protein PstB2p (PtdSer transport B pathway protein encoded by the PSTB2 gene that complements the pstB2 mutation affecting PtdSer transport), must be present on acceptor membranes for PtdSer transport to occur. In addition, the action of the PtdIns 4-kinase, Stt4p (PtdIns 4-kinase encoded by the STT4 gene that complements the stt4 mutation causing staurosporine and temperature-sensitive growth) is also required for PtdSer transport to the locus of Psd2p. Reconstitution of PtdSer transport to Psd2p using liposomes demonstrates that PtdSer-rich domains present in vesicles are preferred substrates for transport. In addition, the incorporation of phosphatidic acid into donor membranes enhances the rate of PtdSer transport. Collectively, these data support a model for PtdSer transport in which specific proteins and lipids are required on donor and acceptor membranes.

Aminoglycerophospholipid metabolism

PtdSer (phosphatidylserine), PtdEtn (phosphatidylethanolamine) and PtdCho (phosphatidylcholine) comprise a subgroup of polar lipids known as the aminoglycerophospholipids. Typically, these lipids account for 70–80% of the membrane phospholipids of many eukaryotes [1]. On average, cell membranes contain approx. 50 mol% PtdCho, 20–30 mol% PtdEtn and 5–10 mol% PtdSer. The major site for synthesis of PtdSer is the ER (endoplasmic reticulum). After its synthesis, PtdSer can be transported to the plasma membrane, Golgi apparatus, mitochondria, lysosome or vacuole, and endosomes. In both yeast and mammalian cells, the transport of PtdSer to the mitochondria is accompanied by the import of this lipid to the inner mitochondrial membrane where it serves as a substrate for Psd1p (a phosphatidylserine decarboxylase 1 encoded by the PSD1 gene that complements psd1 mutations), which catalyses the decarboxylation to PtdEtn [2]. Yeast expresses a second enzyme, Psd2p, which decarboxylates PtdSer arriving at the Golgi to form PtdEtn [3,4]. The PtdEtn formed by the decarboxylation reactions in either the mitochondria or the Golgi can be exported from these organelles back to the ER where it is further metabolized to PtdCho [5]. It is not clear why the eukaryotic membrane systems evolved to spatially and temporally segregate the processes of PtdSer synthesis and decarboxylation. However, this segregation of enzymes enables investigators to exploit the situation, and use the decarboxylation of PtdSer as a specific biochemical indicator of lipid transport between the ER and the mitochondria or Golgi [6]. A schematic outline of this approach is shown in Figure 1.

PtdSer transport and metabolism in eukaryotes

Figure 1
PtdSer transport and metabolism in eukaryotes

The routes of PtdSer transport for the purpose of PtdEtn synthesis are shown. PtdSer transport to the mitochondria is designated as the PSTA pathway. PtdSer transport to the Golgi is designated as the PSTB pathway. The PSTA pathway is operative in yeast and mammalian cells and the PSTB pathway has so far only been described in yeast. The generation of PtdEtn in the mitochondria and the Golgi by PtdSer decarboxylases (Psd1p and Psd2p) serves as a biochemical indicator that PtdSer transport to the organelles has occurred. The actions of Psd1p and Psd2p can also serve as the basis for genetic screens for mutant strains defective in PtdSer transport. Mutants selectively deficient in the PSTA pathway have been described in both mammalian and yeast cells. Mutants selectively deficient in the PSTB pathway have been described in yeast.

Figure 1
PtdSer transport and metabolism in eukaryotes

The routes of PtdSer transport for the purpose of PtdEtn synthesis are shown. PtdSer transport to the mitochondria is designated as the PSTA pathway. PtdSer transport to the Golgi is designated as the PSTB pathway. The PSTA pathway is operative in yeast and mammalian cells and the PSTB pathway has so far only been described in yeast. The generation of PtdEtn in the mitochondria and the Golgi by PtdSer decarboxylases (Psd1p and Psd2p) serves as a biochemical indicator that PtdSer transport to the organelles has occurred. The actions of Psd1p and Psd2p can also serve as the basis for genetic screens for mutant strains defective in PtdSer transport. Mutants selectively deficient in the PSTA pathway have been described in both mammalian and yeast cells. Mutants selectively deficient in the PSTB pathway have been described in yeast.

Assay systems for measuring transport

The formation of PtdSer and PtdEtn can be monitored in intact cells, isolated organelles and permeabilized cells using radiolabelled serine as the phospholipid precursor. With this method, the conversion of nascent PtdSer (formed by the PtdSer synthase reaction) into PtdEtn, serves as a measure of lipid transport. When [3H]serine is used as the precursor, the reactions are terminated by lipid extraction and the radioactive products are separated by TLC and quantified by liquid scintillation spectrometry. When [1-14C]serine is used as the precursor, the 14CO2 generated by the decarboxylase reactions can be chemically trapped, and quantified by liquid scintillation spectrometry. The approaches can be modified with permeabilized cells and isolated organelles to prelabel the PtdSer pool and subsequently measure the transport to Psd1p or Psd2p, uncoupled from PtdSer synthesis [7,8]. More recently, methods have been developed to use chemically defined donor membranes in the form of liposomes containing Ptd[1′-14C]serine and acceptor membranes consisting of purified organelle fractions [6,9]. The measurement of selective transport of PtdSer to either Psd1p or Psd2p is accomplished by using mutant strains (psd1Δ or psd2Δ) that are deleted for either of the two genes. Thus decarboxylation of PtdSer in a psd2Δ strain reports transport of the lipid to Psd1p, and the same reaction in a psd1Δ strain reports transport of the lipid to Psd2p.

Genes and proteins controlling interorganelle PtdSer transport

Eukaryotic cells possess multiple pathways for the synthesis of PtdEtn [10]. Two of these pathways are via the PtdSer decarboxylases described above. A third pathway, often called the Kennedy pathway, begins with ethanolamine (Etn) and proceeds through the intermediates phosphoethanolamine (PEtn) and cytidine diphosphate-ethanolamine (CDP-Etn) and finally produces PtdEtn. Empirically, one observes that yeast psd1Δ psd2Δ mutants lacking both PtdSer decarboxylases are non-viable unless they are supplemented with Etn [3]. PtdEtn is known to be essential for the growth of yeast, and Etn supplementation in psd1Δ psd2Δ strains fulfils this requirement by permitting synthesis via the Kennedy pathway [11,12]. These properties of yeast have enabled the isolation of PtdSer transport defective strains by screening for Etn auxotrophs in either a psd1Δ or a psd2Δ genetic background [6]. Strains that are defective in transporting PtdSer to Psd1p, and that also harbour a psd2Δ mutation, are similar to psd1Δ psd2Δ strains and require Etn for growth. Likewise, strains that are defective in transporting PtdSer to Psd2p, and that also have a psd1Δ mutation, exhibit properties almost identical with psd1Δ psd2Δ strains and also require Etn for growth. For simplicity, the transport of PtdSer to Psd1p is referred to as PSTA pathway (a PtdSer transport A pathway), and the transport of PtdSer to Psd2p is referred to as the PSTB pathway.

A mutant strain, designated pstA1 (where pstA is a mutation affecting PtdSer transport in the A pathway), defective in the transport of PtdSer to Psd1p has been isolated and characterized [7]. The pstA1 strain was isolated as an Etn auxotroph after mutagenesis of parental strains harbouring a psd2Δ mutation. The mutant strain exhibits a deficiency in PtdEtn synthesis from PtdSer but has normal levels of PtdSer synthase and PtdSer decarboxylase enzymes. In vitro assays demonstrate that PtdSer synthesized in the MAM (mitochondrial-associated membrane) is imported into the mitochondria of the pstA1 mutant at approx. 30% of the rate found for wild-type strains. The mitochondria of the pstA1 strain have abnormally high density that is readily visualized macroscopically as a novel organelle band on sucrose density gradients. The high density of the mitochondria is consistent with a defect in phospholipid import and reduced PtdEtn content of the organelle. The gene complementing the pstA1 growth defect (Etn auxotrophy) and the lipid transport defect was identified as MET30 [7,13]. The MET30 gene encodes the protein Met30p (a ubiquitin ligase subunit encoded by the MET30 gene that complements the met30 mutation affecting methionine biosynthesis) that is a subunit of SCF (Skp1/Cul1/F-box protein)-ubiquitin ligase [14]. The function of Met30p is the recognition of substrates to which the SCF complex transfers ubiquitin moieties. Studies of Met30p independent of those conducted with the pstA1 mutant, identified the transcription factor Met4p (a transcription factor encoded by the MET4 gene that complements the met4 mutation affecting methionine biosynthesis) as one of the substrates recognized by the ubiquitin ligase [15,16]. Examination of the pstA1 mutant reveals that it is also defective in the ubiquitination of the transcription factor Met4p [7]. In addition, met30 mutants isolated independently of pstA1 exhibit defects in PtdEtn synthesis and show increased mitochondrial density. Collectively, these results indicate that ubiquitination of proteins that serve as substrates for Met30p regulates PtdSer transport from the MAM to the mitochondria.

Reconstitution studies with MAM and mitochondria from mutant and wild-type cells reveal some interesting properties of pstA1 mutants [7]. The in vitro transport reactions utilize MAM as the donor of PtdSer, and mitochondria as the acceptor organelle. The organelles can be prepared independently from mutant and wild-type strains. As outlined in Figure 2, when MAM and mitochondria are derived from wild-type cells, PtdSer transport readily occurs between the two organelles. However, MAM derived from pstA1 cells is defective as a donor of PtdSer to wild-type mitochondria. In addition, mitochondria derived from pstA1 strains are defective as acceptors for PtdSer transport from wild-type MAM. When both the MAM and mitochondria are derived from pstA1 strains, both the donor and acceptor membranes are incompetent for lipid transport. From these findings, we conclude that the pstA1 defect resides on both the MAM and the mitochondria. Our current working hypothesis is that specific proteins reside on both the donor and the acceptor membranes that participate in docking and/or transport of PtdSer between the organelles. These proteins are represented schematically in Figure 2 by small hexagons. The expression, activity or the ubiquitination of these putative proteins appears to be under the control of Met30p. Ongoing research efforts are now designed to determine how Met30p regulates PtdSer transport to the mitochondria.

Genetic and biochemical analysis of PtdSer transport along the PSTA pathway in yeast

Figure 2
Genetic and biochemical analysis of PtdSer transport along the PSTA pathway in yeast

A summary of key experiments examining the effects of pstA1 mutations on reconstituted PtdSer transport to yeast mitochondria is shown. MAM and mitochondria (MTO) were isolated from wild-type (wt) and mutant (pstA1) yeast. The MAM fractions were incubated under conditions that produce radioactive PtdSer that is subsequently transported to the mitochondria and decarboxylated to form PtdEtn. Wild-type cells are competent to transport PtdSer to mitochondria, but pstA1 mutants are defective in the transport reaction as indicated in the Figure. In addition, incubation of pstA1 MAM with wild-type mitochondria, or wild-type MAM with pstA1 mitochondria also fails to produce PtdEtn demonstrating that PtdSer transport is defective in both organelles. Thus the pstA1 mutation produces defects on both the donor and acceptor sides of the interorganelle transport reaction. The proteins present on the MAM (donor) and mitochondria (acceptor) that are affected by the pstA1 mutation are shown schematically as hexagons.

Figure 2
Genetic and biochemical analysis of PtdSer transport along the PSTA pathway in yeast

A summary of key experiments examining the effects of pstA1 mutations on reconstituted PtdSer transport to yeast mitochondria is shown. MAM and mitochondria (MTO) were isolated from wild-type (wt) and mutant (pstA1) yeast. The MAM fractions were incubated under conditions that produce radioactive PtdSer that is subsequently transported to the mitochondria and decarboxylated to form PtdEtn. Wild-type cells are competent to transport PtdSer to mitochondria, but pstA1 mutants are defective in the transport reaction as indicated in the Figure. In addition, incubation of pstA1 MAM with wild-type mitochondria, or wild-type MAM with pstA1 mitochondria also fails to produce PtdEtn demonstrating that PtdSer transport is defective in both organelles. Thus the pstA1 mutation produces defects on both the donor and acceptor sides of the interorganelle transport reaction. The proteins present on the MAM (donor) and mitochondria (acceptor) that are affected by the pstA1 mutation are shown schematically as hexagons.

The second arm of the transport pathways shown in Figure 1 illustrates PtdSer transport to the locus of Psd2p in the Golgi. Genetic screening for mutations in this pathway has produced three interesting mutants. These mutants are designated pstB1, pstB2 and psd2-C2Δ [mutation in which the C2 (Ca2+ and phospholipid-binding sequence) domain of Psd2p is deleted]. All three mutants are Etn auxotrophs in a psd1Δ genetic background. A summary of the sites of action of the gene products encoded by genes that complement these mutants appears in Figure 3. The pstB1 mutant exhibits a modest defect in the transport-dependent conversion of nascent PtdSer into PtdEtn by Psd2p [17]. The gene that complements the growth defect and restores normal PtdSer transport is STT4, which encodes a PtdIns 4-kinase [18]. The precise role performed by the product of the kinase reaction, PtdIns4P, remains to be elucidated. The current hypothesis is that this lipid serves as a recognition signal on the donor membrane for the assembly of protein factors involved in PtdSer transport. These protein factors may be involved in forming lipid microdomains necessary for PtdSer transport, or in the assembly of docking proteins that enable the attachment of the donor and the acceptor membranes.

Genetic and biochemical analysis of PtdSer transport by the PSTB pathway in yeast

Figure 3
Genetic and biochemical analysis of PtdSer transport by the PSTB pathway in yeast

This Figure summarizes major features of elements associated with the donor and acceptor membranes deduced from in vivo studies, and in vitro reconstitution experiments. The PtdIns 4-kinase, Stt4p, is required for PtdSer transport to Psd2p. The PtdIns4P is proposed to play a role in the donor membrane, either by facilitating the organization of PtdSer domains or interacting with proteins on the acceptor membrane to promote the docking between membranes. PtdSer domains have been implicated from reconstitution studies with liposomes that also demonstrate that PtdOH can enhance PtdSer transport to Psd2p. PstB2p is an amphitropic lipid-binding protein that must be present on the acceptor for PtdSer transport to occur. The C2 domain of Psd2p is not essential for catalysis but is required for PtdSer transport from the donor to the acceptor membrane.

Figure 3
Genetic and biochemical analysis of PtdSer transport by the PSTB pathway in yeast

This Figure summarizes major features of elements associated with the donor and acceptor membranes deduced from in vivo studies, and in vitro reconstitution experiments. The PtdIns 4-kinase, Stt4p, is required for PtdSer transport to Psd2p. The PtdIns4P is proposed to play a role in the donor membrane, either by facilitating the organization of PtdSer domains or interacting with proteins on the acceptor membrane to promote the docking between membranes. PtdSer domains have been implicated from reconstitution studies with liposomes that also demonstrate that PtdOH can enhance PtdSer transport to Psd2p. PstB2p is an amphitropic lipid-binding protein that must be present on the acceptor for PtdSer transport to occur. The C2 domain of Psd2p is not essential for catalysis but is required for PtdSer transport from the donor to the acceptor membrane.

The pstB2 mutant strain has a very severe defect in the transport of nascent PtdSer to Psd2p [19]. The gene that complements the growth and lipid transport defect of the mutant is PSTB2. The PSTB2 gene has also been identified in other genetic studies and is alternatively designated SFH4 and PDR17 [20,21]. We use the PSTB2 nomenclature for consistency in this article. The protein encoded by this gene, PstB2p (PtdSer transport B pathway protein encoded by the PSTB2 gene that complements the pstB2 mutation affecting PtdSer transport), has sequence similarity to the PtdIns/PtdCho transfer protein, Sec14p (PtdIns/PtdCho transfer protein that is encoded by the SEC14 gene that complements sec14 mutant affecting protein secretion) [22,23]. Like Sec14p, PstB2p can bind and transfer PtdIns between membranes in vitro [19]. In addition, overexpression of PSTB2 can suppress the lethality of sec14ts mutations. However, overexpression of SEC14 does not suppress pstB2 mutations. Although the PstB2p is involved in the process of PtdSer transport between membranes in vivo, there is no evidence to demonstrate that it acts as a soluble carrier of PtdSer in vitro. PstB2p is amphitropic, and found in both soluble and membrane-associated forms in yeast cells. Reconstitution studies measuring PtdSer transport to Psd2p demonstrate that PstB2p must be associated with the acceptor membrane for lipid transport to occur. This latter property of PstB2p is most intriguing and is consistent with the idea that it interacts with specific proteins and/or lipids on the acceptor membrane to form a complex involved in PtdSer transport. Current work with PstB2p is now focused on defining the full repertoire of lipids and proteins with which it interacts and determining if it is part of a genuine macromolecular complex that forms between donor and acceptor membranes.

The third mutant strain identified in the PSTB pathway is psd2-C2Δ [24]. This mutant strain was developed as part of a probe into the structure and function of Psd2p. Among the structural features of Psd2p is a C2 domain. C2 domains were first described for protein kinase C as Ca2+ and phospholipid-binding regions of the protein. Numerous C2 domains have now been described in many proteins and these domains participate in both lipid and protein recognition events, and frequently membrane attachment by soluble proteins [25,26]. To investigate the role of the C2 domain in Psd2p function, this region of the protein was deleted to generate the psd2-C2Δ strain [24]. The protein produced by this manipulation is designated Psd2-C2Δp. Overexpression of Psd2-C2Δp from a high copy plasmid in a psd1Δ psd2Δ genetic background that is otherwise devoid of PtdSer decarboxylase activity, demonstrates that the C2 domain is not required for catalytic activity of the enzyme. The overexpression enables the protein to be produced at 10–20 times the level required for cell growth. In addition, subcellular fractionation reveals that Psd2-C2Δp is localized normally within the cell. However, despite the high level of expression of Psd2-C2Δp, this enzyme cannot support the growth of yeast strains harbouring psd1Δ psd2Δ mutations. Strains expressing Psd2-C2Δp as the only PtdSer decarboxylase accumulate PtdSer and fail to synthesize significant levels of PtdEtn. Reconstitution studies further demonstrate that donor membranes are unable to transfer PtdSer to the Psd2-C2Δp present in acceptor membranes. Collectively, these studies implicate the C2 domain of Psd2p in the transport of PtdSer between the donor and the acceptor membranes. The mechanism by which the C2 domain of Psd2p functions remains to be elucidated. The C2 domain could participate in docking and/or transport complexes formed between the donor and acceptor membranes. Since C2 domains participate in both lipid and protein recognition phenomena, either class of molecule could contribute to interactions between the membranes.

Lipid participation in PtdSer transport

In addition to the role of proteins in regulating PtdSer transport, there is growing evidence that phospholipids also have an important function in the process. Recent evidence suggests that specialized domains of PtdSer may be an integral part of donor and acceptor membrane recognition and lipid transport. In reconstitution studies with liposomes as donors and Psd2p-containing membranes as acceptors, a striking requirement for PtdSer-rich domains as substrates for transport was observed [9]. Liposomes composed of 100 mol% PtdSer efficiently interact with acceptor membranes and act as competent donors. However, liposomes composed of 50% PtdSer and 50% PtdCho are incompetent as donors. This effect appears only due to the surface dilution of PtdSer within the plane of the bilayer, consistent with the idea that specialized PtdSer domains are required for lipid transport. PtdEtn and PtdIns have similar effects to PtdCho as inhibitors of PtdSer transport from liposomes to Psd2p. In contrast, surface dilution by PtdOH (phosphatidic acid) does not inhibit PtdSer transport and under some conditions stimulates the process. The effect of surface dilution by PtdIns4P is also notably different from PtdCho and maintains PtdSer transport, but at a lower level than found with PtdOH. This latter result is most interesting because the genetic experiments described earlier implicate the PtdIns 4-kinase, Stt4p (PtdIns 4-kinase encoded by the STT4 gene that complements the stt4 mutation causing staurosporine and temperature-sensitive growth), as an important element in PtdSer transport. The role of phospholipids as regulators of PtdSer transport was unanticipated and their mechanism of action remains to be elucidated. Current models for the interplay between donor and acceptor membranes and their respective protein and lipid components in the PSTB pathway are highly speculative. One model that is consistent with current experimental results proposes that the C2 domain of Psd2p, and PstB2p present on the acceptor membrane, can interact with phospholipids on the donor membrane such as PtdSer, PtdOH and PtdIns4P. This interaction between the proteins and selected anionic lipids may orchestrate segregation of PtdSer away from the bulk phospholipid on the donor, creating the PtdSer-rich domains that function as effective substrates for transport. A complex of Psd2p and PstB2p and perhaps other (as yet unidentified) proteins on the acceptor membrane functions as the PtdSer transport machinery that moves the lipid between the membranes.

Future directions

Intermembrane phospholipid transport is one of the most fundamental processes of membrane biogenesis. Currently, there is a paucity of genetic and biochemical information about the components that participate in phospholipid transport, their mechanisms of action and their regulation. The metabolism of PtdSer to PtdEtn has provided a tractable biochemical and genetic route for examining phospholipid transport. Current findings implicate protein ubiquitination in the PSTA pathway, and a selection of anionic phospholipids (PtdSer, PtdOH and PtdIns4P) and proteins (Stt4p, Psd2 and PstB2) in the PSTB pathway. These biochemical components now appear to be a key in elucidating some of the mechanisms involved in transporting phospholipids. Elements of the PSTA pathway that now need to be resolved include: (i) identification of the ubiquitination substrates for Met30p that participate in controlling PtdSer transport, (ii) identification of protein components on the MAM and mitochondria that participate in docking and transport reactions between the organelles and (iii) development of reconstitution systems between MAM and mitochondria that can provide biochemical insight into the mechanisms for PtdSer transport between the organelles. Examination of the PSTB pathway now needs to be expanded to address the problems of: (i) elucidation of the lipid binding properties of the C2 domain of Psd2p, (ii) elucidation of the lipid binding properties of PstB2p, (iii) identification of protein–protein interactions between Psd2p and PstB2p and other proteins present on donor and acceptor membranes and (iv) elucidation of the roles of PtdOH and PtdIns4P in regulating PtdSer transport. Experimental resolution of the above issues is likely to provide important and novel mechanistic insights into the biochemical machinery that controls phospholipid transport and membrane biogenesis.

Seventh Yeast Lipid Conference: Independent Meeting held at Swansea Clinical School, Swansea, Wales, U.K., 12–14 May 2005. Organized and Edited by D. Kelly, S. Kelly and D. Lamb (Swansea, U.K.).

Abbreviations

     
  • C2

    Ca2+ and phospholipid-binding sequence

  •  
  • ER

    endoplasmic reticulum

  •  
  • MAM

    mitochondria-associated membrane

  •  
  • Met30p

    a ubiquitin ligase subunit encoded by the MET30 gene that complements the met30 mutation affecting methionine biosynthesis

  •  
  • Met4p

    a transcription factor encoded by the MET4 gene that complements the met4 mutation affecting methionine biosynthesis

  •  
  • PtdSer

    phosphatidylserine

  •  
  • Psd1p

    phosphatidylserine decarboxylase 1 encoded by the PSD1 gene that complements psd1 mutations

  •  
  • psd2-C2Δ

    mutation in which the C2 domain of Psd2p is deleted

  •  
  • pstA(pstB)

    mutation affecting PtdSer transport in the A (B) pathway

  •  
  • PSTA (PSTB) pathway

    PtdSer transport A (B) pathway

  •  
  • PstB2p

    PSTB protein encoded by the PSTB2 gene that complements the pstB2 mutation affecting PtdSer transport

  •  
  • PtdCho

    phosphatidylcholine

  •  
  • PtdEtn

    phosphatidylethanolamine

  •  
  • PtdOH

    phosphatidic acid

  •  
  • SCF

    Skp1/Cul1/F-box protein

  •  
  • Sec14p

    PtdIns/PtdCho transfer protein that is encoded by the SEC14 gene that complements sec14 mutant affecting protein secretion

  •  
  • Stt4p

    PtdIns 4-kinase encoded by the STT4 gene that complements the stt4 mutation causing staurosporine and temperature-sensitive growth

This work was supported by the National Institutes of Health Merit Award 2R37 GM32453.

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