Microtubule motor proteins play key roles in the spatial organization of intracellular organelles as well as the transfer of material between them. This is well illustrated both by the vectorial transfer of biosynthetic cargo from the endoplasmic reticulum to the Golgi apparatus as well as the sorting of secretory and endocytic cargo in the endosomal system. Roles have been described for dynein and kinesin motors in each of these steps. Cytoplasmic dynein is a highly complex motor comprising multiple subunits that provide functional specialization. The family of human kinesins includes over 40 members. This complexity provides immense functional diversity, yet little is known of the specific requirements and functions of individual motors during discrete membrane trafficking steps. In the present paper, we describe some of the latest findings in this area that seek to define the mechanisms of recruitment and control of activity of microtubule motors in spatial organization and cargo trafficking through the endosomal network.

Introduction

Eukaryotic cells are compartmentalized into distinct organelles that are composed of specific cohorts of proteins and lipids. Precise transport mechanisms are therefore required to direct molecules to the right compartment, to generate and maintain their identity and their specific functions. An elegant example of the complexity and functional specialization of related membranous organelles comes from the endosomal network. This system consists not only of distinct organelles but also of discrete membrane domains within organelles; it also underpins essential cell functions, including the control of growth factor and morphogen signalling, cell adhesion and migration, and functional specializations such as the formation of dendritic spines and primary cilia. In this review, we focus on the role of microtubule-based motor proteins in endosomal sorting and give an update on their close relationships with different key players of endosomal sorting, including SNXs (sorting nexins) and Rab proteins.

Endosomal sorting

Endocytosis is the process by which cells internalize molecules from the cell surface. Endocytic vesicles initially mature and either homotypically fuse, or fuse with pre-existing organelles known historically as EEs (early endosomes), now more commonly referred to as SEs (sorting endosomes) [1]. Here sorting events direct cargoes either to recycling pathways back to the plasma membrane or to a degradative pathway via late endosomes and lysosomes. Other cargoes are ultimately delivered to the TGN (trans-Golgi network). In its simplest form, this system can be considered to comprise SEs, recycling endosomes, multivesicular bodies and lysosomes [2]. These primary endosomal trafficking pathways are summarized in Figure 1. The machinery used to drive these pathways can be defined according to the localization of key molecular markers including the phosphoinositide phospholipids, Rab proteins and SNXs [3].

Endosomal trafficking pathways

Figure 1
Endosomal trafficking pathways

This schema summarizes the primary endosomal trafficking pathways. The different compartments are indicated in grey and transport steps are represented by arrows. Clathrin coat is depicted in red. Endocytosis pathways are represented in purple, recycling pathways are in green, the degradation pathway is in orange and retromer transports are in blue. Other pathways and coat proteins exist, but are not depicted.

Figure 1
Endosomal trafficking pathways

This schema summarizes the primary endosomal trafficking pathways. The different compartments are indicated in grey and transport steps are represented by arrows. Clathrin coat is depicted in red. Endocytosis pathways are represented in purple, recycling pathways are in green, the degradation pathway is in orange and retromer transports are in blue. Other pathways and coat proteins exist, but are not depicted.

After their incorporation in the SE, receptors are sent back to the plasma membrane, to the late endosome or to the ERC (endocytic recycling compartment). There are two main recycling pathways back to the plasma membrane from the SE. Some cargoes are recycled directly to the plasma membrane [4], whereas others are recycled via the ERC [5]. Rab proteins are small GTPases and play essential regulatory roles in intracellular trafficking pathways. Rab4 and Rab5 are localized to a fast recycling pathway, whereas a slower recycling pathway is defined by Rab4 and Rab11 [6]. The ERC also plays a role in the retrograde transport to the TGN [1]. A key player in endosomal sorting is the retromer complex, a multiprotein complex that associates with endosomes and mediates retrograde transport from the SE to the TGN [7]. In mammals, the retromer pathway includes an SNX dimer (SNX1 or SNX2 with SNX5 or SNX6) and a cargo recognition trimer Vps26–Vps29–Vps35 [7,8]. Sorting of cargo to the TGN occurs via a tubulation event where the membrane deformation potential of the SNX proteins is central [8]. Increasing evidence suggests that members of the SNX family are key factors in defining the organization and dynamics of the endosomal network. Their ability to deform membranes is likely to be central to their ability to mediate selective trafficking through this network.

Microtubule-based motor proteins in the endosomal system

Evidence exists that different cargoes are sorted into distinct populations of clathrin-coated vesicles, a notable example being the sorting of G-protein-coupled receptors [9]. Other work has suggested that cargoes destined for degradation are targeted preferentially to rapidly maturing SE, whereas those destined for recycling are targeted to all vesicles [10]. One potential mechanism driving cargo sorting within this system is the integration between certain endocytic adaptors and microtubule-dependent motility. Considerable further evidence also implicates motors in endocytic sorting.

Microtubule-based motor proteins are required for intracellular movements, organization and positioning of membrane-bound organelles (recently reviewed in [11]). In Dictyostelium, dynein and kinesin have been shown to be both required for the bidirectional movements of endosomes [12]. Kinesin-1, involved in the EE movements, and kinesin-2, requisite for early and late endosome movements, are indeed the major motors [13]. Opposing motors dynein and kinesin-3 have been shown to be both required for retrograde and anterograde movements of SE, the direction of transport being driven by dynein binding to the organelle [14].

KIF13A (kinesin family member 13A) or kinesin-3 has been shown to interact with the clathrin-adaptor-1 or AP-1 (adaptor protein 1) and this interaction promotes the formation of the peripheral recycling compartment in melanocytes [15]. KIF16B (also called SNX23) is another member of kinesin-3 subfamily that drives SE movements towards the cell periphery and also is essential for modulating the balance between receptor recycling and degradation. Interestingly, this specific kinesin, a member of the SNX family, is localized to the PtdIns3P-enriched EE membranes via its PX (Phox homology) domain [16], suggesting a mechanism of direct coupling of the motor to the membrane.

Opposing motors also contribute to the separation of tubular and vesicular endosomal subdomains, thus are key players during the sorting process. EGF (epidermal growth factor) receptor, destined to the degradation pathway and transferrin receptor, destined to the recycling pathway, enter the same SEs and microtubule-based motor dynein is required for the efficient separation of these cargos within the SE [17]. With such body of evidence placing both dynein and kinesin motor proteins at the EE, with specific roles for different family members, microtubule-based motors are suggested to play a key role in defining the specificity of cargo sorting during endosomal sorting.

Given that transport from the cell cortex to the juxtanuclear region is minus-end-directed, a key player in these trafficking events is clearly the dynein motor. A core role for this motor in the motility of endosomal and lysosomal compartments is well supported in the literature [1822]. More recent data have focused on the individual components of dynein and how this single motor could define such a complex array of trafficking pathways. The multisubunit nature of the dynein complex leads one to postulate about the potential for selective targeting of this motor to different membranes. Furthermore, data also suggest that its partner complex, dynactin [23], is also involved in directing either the localization or activity of the dynein complex through interaction with other membrane-bound protein complexes [21,22,24]. One focus for this work has been the dynein LIC1 (light intermediate chain 1) and LIC2. Homodimerization of these subunits [25] therefore specifies LIC1- or LIC2-containing subpopulations of dynein. Work from our own laboratory using siRNA (small interfering RNA) depletion of these subunits revealed LIC1 to act primarily in the organization of the ER (endoplasmic reticulum)/Golgi interface, notably in maintaining the structure of the Golgi. In contrast, LIC2 was implicated in positioning of recycling endosomes [26]. It is important to note here that our work was focused on the use of transferring as a reporter of the recycling endosomes and did not include any analysis of other endosomal markers [26]. However, other work has defined a role for LIC1 and LIC2 in dynein recruitment to late endosomes and lysosomes [27]. Data support the idea of LIC specificity: pericentrin binds to LIC1 but not LIC2 [25], whereas LIC2, but not LIC1, appears to interact with PAR3 to define a functional complex involved in cell polarization [28]. Other work has shown a differential localization of LIC1 and LIC2 as cell progress through mitosis [29]. Rab11 also appears to direct dynein recruitment through its effector FIP3 (Rab11 family-interacting protein 3), but here no LIC specificity is evident [30,31]. These data could be reconciled in many ways. It is highly likely that only one (or at most a few) dyneins are involved in organelle movement (Steinberg's laboratory recently showed that in Ustilago maydis, a single dynein is involved in the translocation of EEs [14]). Cell-type differences as well as the efficacy of siRNA depletions might explain differences in the effects on Golgi organization on LIC depletion. Our more recent data support a selective role for the LICs in individual membrane trafficking steps, even within the complex endosomal network (S.D. Hunt and D.J. Stephens, unpublished work).

The importance of bidirectional transport

Nearly all cargos are transported bidirectionally, and little is known about the co-ordination between opposing motors. For many cargos, interference with their plus- or minus-directed motor protein completely disrupts their movement, suggesting a strong link between dynein and kinesin. Bidirectional movements have been described previously for ERES (ER exit sites) and were proved to be driven by microtubule-associated motor proteins [32]. Whether bidirectional movements are due to a motor co-ordination or a tug-of-war between opposing motors is still hotly discussed and probably depends on the system under investigation [33,34]. With multiple examples of specific associations of motor proteins with certain cargo (e.g. [14,34]), one might consider these associations being the key role of microtubule-based motors in defining the specificity of cargo sorting during endosomal sorting.

Rab proteins and microtubule-based motor proteins

Rab proteins are crucial endocytic regulators. These small GTP-binding proteins cycle between an inactive GDP-bound state and an active GTP-bound state. In their active state, they are interacting and recruiting proteins known as Rab effectors. The latter have many roles, including vesicle tethering, fusion, budding and motility [35]. Major populations of endosome have been identified that label with a mosaic of Rab4, Rab5, Rab7 and Rab11 positive. Rab4 and Rab5 define EEs/SEs, whereas the Rab11 is classically used to describe the juxtanuclear recycling endosome [35]. Rab7 and Rab9 are late endosomal markers. EE matures into late endosome via a process of morphological changes. Contents from EE to late endosome switch between different markers (Rab5 to Rab7) and the composition of the phospholipids layer also undergoes changes [PtdIns3P to PtdIns(3,5)P2] [36]. Rab proteins and their effectors are not only required for budding and fusion events but they also regulate movements of vesicles and organelles along microtubules and actin filaments; see [37]. An increasing amount of evidence shows associations between these small GTPase and microtubule-based motors (Table 1). Rab proteins are therefore determinants on the directionality of vesicle movements. Table 1 provides some principal examples of Rab motor coupling; many other Rabs are known to couple to kinesin family members as well as dynein and also myosin superfamily motors (for some good examples, see [37]).

Table 1
Some key examples of coupling of Rabs to motors

KIFC1, kinesin family member C1; RILP, Rab-interacting lysosomal protein.

Rab Function 
Rab1A Rab1a regulates the motility of early endocytic vesicles by recruiting the motor KIFC1 to these vesicles [46
Rab4 Rab4, for instance, interacts with kinesin-2 and directly with microtubules, interactions that are crucial for the exocytosis of specific cargos [47
Rab5 Rab5 regulates the entry of cargo from the plasma membrane, the generation of PtdIns3P, and the motility of the SE on actin and microtubules tracks. The major role of Rab5 is to promote membrane tethering and fusion of endocytic vesicles with the SE [6,35]. Rab5 is also clearly implicated in motility of early endosomes: Rab5 and PtdIns3P are both required for the recruitment of Kif16B to EEs [16]. Dynein-dependent transport of Rab5-positive endosomes is also important in neuronal branching [48
Rab7 Rab7 associates with late endosome/lysosome compartments and controls transport in these compartments. Involved in the regulation of EGF and EGFR (EGF receptor) degradation, along with Rab5, Rab7 is also as a key regulator in the recruitment of the retromer complex at the EE [49]. Rab7 effector, involved in late endosome motility (RILP), recruits dynein motor and control lysosomal transport by preventing further cycling of Rab7; consequently, late endosome and lysosome are transported by microtubule-based motors towards microtubule minus ends [50
Rab11 The Rab11 effector protein FIP3 binds dynein light chain 2 and form a complex with Rab11 and dynein that mediates transport to the ERC [30,31
Rab Function 
Rab1A Rab1a regulates the motility of early endocytic vesicles by recruiting the motor KIFC1 to these vesicles [46
Rab4 Rab4, for instance, interacts with kinesin-2 and directly with microtubules, interactions that are crucial for the exocytosis of specific cargos [47
Rab5 Rab5 regulates the entry of cargo from the plasma membrane, the generation of PtdIns3P, and the motility of the SE on actin and microtubules tracks. The major role of Rab5 is to promote membrane tethering and fusion of endocytic vesicles with the SE [6,35]. Rab5 is also clearly implicated in motility of early endosomes: Rab5 and PtdIns3P are both required for the recruitment of Kif16B to EEs [16]. Dynein-dependent transport of Rab5-positive endosomes is also important in neuronal branching [48
Rab7 Rab7 associates with late endosome/lysosome compartments and controls transport in these compartments. Involved in the regulation of EGF and EGFR (EGF receptor) degradation, along with Rab5, Rab7 is also as a key regulator in the recruitment of the retromer complex at the EE [49]. Rab7 effector, involved in late endosome motility (RILP), recruits dynein motor and control lysosomal transport by preventing further cycling of Rab7; consequently, late endosome and lysosome are transported by microtubule-based motors towards microtubule minus ends [50
Rab11 The Rab11 effector protein FIP3 binds dynein light chain 2 and form a complex with Rab11 and dynein that mediates transport to the ERC [30,31

SNXs and microtubule-based motor proteins

The composition in phosphoinositides at the SE is controlled at least in part by Rab5. The phosphoinositides play a major role in defining endosomal identity through specifying recruitment of effector molecules, including motor proteins (Rab5, for example, see Table 1). This defined identity is also crucial for the selective recruitment of SNXs. Thus the relationship between Rabs and SNXs is likely to dictate a further layer of complexity in terms of motor coupling.

SNXs

The SNX family is a group of cytoplasmic and membrane-associated proteins involved in protein and membrane trafficking [3]. SNXs are all characterized by the presence of a specific type of domain, the PX domain, a sequence of 100–130 amino acids [38]. These particular domains are phosphoinositide-binding motifs that help the association between their host protein and the membranes enriched in these lipids. PX domains have been shown to mostly interact with PtdIns3P, a lipid present on the cytosolic face of endosomes. This ability to bind certain lipids is a key part of the mechanism of targeting these proteins to cellular membranes. Some SNXs also contain a BAR domain (Bar/amphiphysin/Rvs) that binds to a highly curved membrane, or can impose curvature upon membranes, inducing the generation of tubulovesicular elements. These proteins form a subfamily, also called SNX–BARs [8], where the PX and BAR domains co-operate in membrane targeting through coincidence detection (see, e.g., [39,40]). The ability of SNXs to associate with PtdIns3P-enriched membrane of the early endocytic network, drive membrane deformation and couple to microtubule motors, makes them central players in driving endosomal dynamics [3].

Co-ordination of endosomal sorting and motor proteins

Endosomal sorting is thought to be orchestrated by complex interactions between SNXs, cargo and many other components. Cargo sorting occurs within tubular subdomains of interconnected organelle membranes. Tubulation here provides a potential mechanism for geometric sorting where cargo segregates into tubules purely on the basis of membrane area. One of the tubular elements enriched in SNX–BARs is the ETC (endosome-to-TGN transport carrier) that is characterized by the presence of SNX1. SNX1 and SNX4 may be both in the same EE compartment but they generate distinct tubules [3]. It is possible that interactions between dynein and different SNXs together co-ordinate endosomal sorting [36]; there might also be roles for other motor proteins in SNX-mediated sorting events. Both SNX1 and SNX4 couple to dynein yet operate within discrete transport pathways. SNX1 is a retromer component dictating transport of cargo from endosome to TGN, whereas SNX4 is involved in transferrin receptor recycling (also called the bulk recycling pathway). Interestingly, SNX4 has also been shown to interact with clathrin and dynein; after the release of clathrin, dynein could bind SNX4 and mediate retrograde transport to the Golgi; hence, the suggested role for clathrin as a regulator of SNX4-dependent transport [41]. One possible explanation for this is that the SNXs couple via distinct adaptor molecules, SNX4 via KIBRA to dynein [40], whereas SNX1 binds dynactin [42].

Molecular motors are thought to drive fission events as well as transporting cargo-loaded carrier to the recipient membrane. Mammalian retromer function includes SNX1/SNX2 and SNX5/SNX6; these proteins could act to generate a tubular subdomain within the EE providing a nucleation point for tubule formation. Indeed, suppression of dynactin can induce the generation of very long retromer tubules unable to separate from the EE [42]. Tubule-based sorting has also recently been shown to occur to segregate the β2- adrenergic receptor, from bulk recycling proteins and the degrading δ-opioid receptor using an actin- and sequence-dependent mechanism [43]. Whether specific motifs within the cytoplasmic domains of cargo molecules also engage or modulate SNX/motor function remains to be defined. As well as tubulation, the association of SNXs and motor proteins might help drive membrane fission by providing longitudinal tension. This concept of longitudinal tension as a driving force for membrane fission is also a feature of dynamin function [44].

It is highly likely that other SNX proteins have key roles in the endosomal network. For example, SNX8 localizes to EE and partially co-localizes with the retromer complex, its suppression has a direct effect on the retrograde transport endosome-to-TGN trafficking [45], but little is known about the biology and biochemistry of this protein [36]. Whether SNX8 couples to motor proteins remains to be seen. Open questions remain about how many of the SNX proteins might couple to motors and notably whether they couple solely to dynein or to other motors (such as kinesin family members) in addition. GFP (green fluorescent protein) tagging and siRNA depletion means that we have the tools to more generate a ‘motor map’ of the endocytic network and derive more functional data relating to the specific dynein components that are required and the kinesin family members that might also be involved.

Conclusion and perspectives

Highlighted in this review are the multiple specific interactions between specific motor proteins and cargo, SNX and Rab proteins. We suggest these associations being the key mechanism of specific sorting, transports and tethering, placing microtubule-based motor proteins as active players in these specific mechanisms.

Cellular Cytoskeletal Motor Proteins: A Biochemical Society/Wellcome Trust Focused Meeting held at Wellcome Trust Genome Campus, Hinxton, Cambridge, U.K., 30 March–1 April 2011. Organized and Edited by Folma Buss (Cambridge, U.K.) and John Kendrick-Jones (MRC Laboratory of Molecular Biology, Cambridge, U.K.).

Abbreviations

     
  • BAR

    Bar/amphiphysin/Rvs

  •  
  • EE

    early endosome

  •  
  • EGF

    epidermal growth factor

  •  
  • ER

    endoplasmic reticulum

  •  
  • ERC

    endocytic recycling compartment

  •  
  • FIP3

    Rab11 family-interacting protein 3

  •  
  • LIC

    light intermediate chain

  •  
  • PX

    Phox homology

  •  
  • SE

    sorting endosome

  •  
  • siRNA

    small interfering RNA

  •  
  • SNX

    sorting nexin

  •  
  • TGN

    trans-Golgi network

We thank Jan van Weering for a critical reading of this paper before submission. We apologize to those authors whose work we could not cite owing to space limitations.

Funding

Work in the Stephens laboratory was funded by the Medical Research Council.

References

References
1
Hsu
V.W.
Prekeris
R.
Transport at the recycling endosome
Curr. Opin. Cell Biol.
2010
, vol. 
22
 (pg. 
528
-
534
)
2
Maxfield
F.R.
McGraw
T.E.
Endocytic recycling
Nat. Rev. Mol. Cell Biol.
2004
, vol. 
5
 (pg. 
121
-
132
)
3
Cullen
P.J.
Endosomal sorting and signalling: an emerging role for sorting nexins
Nat. Rev. Mol. Cell Biol.
2008
, vol. 
9
 (pg. 
574
-
582
)
4
Deneka
M.
Neeft
M.
Popa
I.
van Oort
M.
Sprong
H.
Oorschot
V.
Klumperman
J.
Schu
P.
van der Sluijs
P.
Rabaptin-5α/rabaptin-4 serves as a linker between rab4 and γ1-adaptin in membrane recycling from endosomes
EMBO J.
2003
, vol. 
22
 (pg. 
2645
-
2657
)
5
van der Sluijs
P.
Hull
M.
Webster
P.
Male
P.
Goud
B.
Mellman
I.
The small GTP-binding protein rab4 controls an early sorting event on the endocytic pathway
Cell
1992
, vol. 
70
 (pg. 
729
-
740
)
6
Jovic
M.
Sharma
M.
Rahajeng
J.
Caplan
S.
The early endosome: a busy sorting station for proteins at the crossroads
Histol. Histopathol.
2010
, vol. 
25
 (pg. 
99
-
112
)
7
Bonifacino
J.S.
Hurley
J.H.
Retromer
Curr. Opin. Cell Biol.
2008
, vol. 
20
 (pg. 
427
-
436
)
8
van Weering
J.R.
Verkade
P.
Cullen
P.J.
SNX-BAR proteins in phosphoinositide-mediated, tubular-based endosomal sorting
Semin. Cell Dev. Biol.
2010
, vol. 
21
 (pg. 
371
-
380
)
9
Puthenveedu
M.A.
von Zastrow
M.
Cargo regulates clathrin-coated pit dynamics
Cell
2006
, vol. 
127
 (pg. 
113
-
124
)
10
Lakadamyali
M.
Rust
M.J.
Zhuang
X.
Ligands for clathrin-mediated endocytosis are differentially sorted into distinct populations of early endosomes
Cell
2006
, vol. 
124
 (pg. 
997
-
1009
)
11
Akhmanova
A.
Hammer
J.A.
III
Linking molecular motors to membrane cargo
Curr. Opin. Cell Biol.
2010
, vol. 
22
 (pg. 
479
-
487
)
12
Soppina
V.
Rai
A.K.
Ramaiya
A.J.
Barak
P.
Mallik
R.
Tug-of-war between dissimilar teams of microtubule motors regulates transport and fission of endosomes
Proc. Natl. Acad. Sci. U.S.A.
2009
, vol. 
106
 (pg. 
19381
-
19386
)
13
Loubery
S.
Wilhelm
C.
Hurbain
I.
Neveu
S.
Louvard
D.
Coudrier
E.
Different microtubule motors move early and late endocytic compartments
Traffic
2008
, vol. 
9
 (pg. 
492
-
509
)
14
Schuster
M.
Lipowsky
R.
Assmann
M.A.
Lenz
P.
Steinberg
G.
Transient binding of dynein controls bidirectional long-range motility of early endosomes
Proc. Natl. Acad. Sci. U.S.A.
2011
, vol. 
108
 (pg. 
3618
-
3623
)
15
Delevoye
C.
Hurbain
I.
Tenza
D.
Sibarita
J.B.
Uzan-Gafsou
S.
Ohno
H.
Geerts
W.J.
Verkleij
A.J.
Salamero
J.
Marks
M.S.
Raposo
G.
AP-1 and KIF13A coordinate endosomal sorting and positioning during melanosome biogenesis
J. Cell Biol.
2009
, vol. 
187
 (pg. 
247
-
264
)
16
Hoepfner
S.
Severin
F.
Cabezas
A.
Habermann
B.
Runge
A.
Gillooly
D.
Stenmark
H.
Zerial
M.
Modulation of receptor recycling and degradation by the endosomal kinesin KIF16B
Cell
2005
, vol. 
121
 (pg. 
437
-
450
)
17
Driskell
O.J.
Mironov
A.
Allan
V.J.
Woodman
P.G.
Dynein is required for receptor sorting and the morphogenesis of early endosomes
Nat. Cell Biol.
2007
, vol. 
9
 (pg. 
113
-
120
)
18
Bomsel
M.
Parton
R.
Kuznetsov
S.A.
Schroer
T.A.
Gruenberg
J.
Microtubule- and motor-dependent fusion in vitro between apical and basolateral endocytic vesicles from MDCK cells
Cell
1990
, vol. 
62
 (pg. 
719
-
731
)
19
Aniento
F.
Emans
N.
Griffiths
G.
Gruenberg
J.
Cytoplasmic dynein-dependent vesicular transport from early to late endosomes
J. Cell Biol.
1993
, vol. 
123
 (pg. 
1373
-
1387
)
20
Burkhardt
J.K.
Echeverri
C.J.
Nilsson
T.
Vallee
R.B.
Overexpression of the dynamitin (p50) subunit of the dynactin complex disrupts dynein-dependent maintenance of membrane organelle distribution
J. Cell Biol.
1997
, vol. 
139
 (pg. 
469
-
484
)
21
Valetti
C.
Wetzel
D.M.
Schrader
M.
Hasbani
M.J.
Gill
S.R.
Kreis
T.E.
Schroer
T.A.
Role of dynactin in endocytic traffic: effects of dynamitin overexpression and colocalization with CLIP-170
Mol. Biol. Cell
1999
, vol. 
10
 (pg. 
4107
-
4120
)
22
Habermann
A.
Schroer
T.A.
Griffiths
G.
Burkhardt
J.K.
Immunolocalization of cytoplasmic dynein and dynactin subunits in cultured macrophages: enrichment on early endocytic organelles
J. Cell Sci.
2001
, vol. 
114
 (pg. 
229
-
240
)
23
Gill
S.R.
Schroer
T.A.
Szilak
I.
Steuer
E.R.
Sheetz
M.P.
Cleveland
D.W.
Dynactin, a conserved, ubiquitously expressed component of an activator of vesicle motility mediated by cytoplasmic dynein
J. Cell Biol.
1991
, vol. 
115
 (pg. 
1639
-
1650
)
24
Blocker
A.
Severin
F.F.
Burkhardt
J.K.
Bingham
J.B.
Yu
H.
Olivo
J.C.
Schroer
T.A.
Hyman
A.A.
Griffiths
G.
Molecular requirements for bi-directional movement of phagosomes along microtubules
J. Cell Biol.
1997
, vol. 
137
 (pg. 
113
-
129
)
25
Tynan
S.H.
Purohit
A.
Doxsey
S.J.
Vallee
R.B.
Light intermediate chain 1 defines a functional subfraction of cytoplasmic dynein which binds to pericentrin
J. Biol. Chem.
2000
, vol. 
275
 (pg. 
32763
-
32768
)
26
Palmer
K.J.
Hughes
H.
Stephens
D.J.
Specificity of cytoplasmic dynein subunits in discrete membrane-trafficking steps
Mol. Biol. Cell
2009
, vol. 
20
 (pg. 
2885
-
2899
)
27
Tan
S.C.
Scherer
J.
Vallee
R.B.
Recruitment of dynein to late endosomes and lysosomes through light intermediate chains
Mol. Biol. Cell
2010
, vol. 
22
 (pg. 
467
-
477
)
28
Schmoranzer
J.
Fawcett
J.P.
Segura
M.
Tan
S.
Vallee
R.B.
Pawson
T.
Gundersen
G.G.
Par3 and dynein associate to regulate local microtubule dynamics and centrosome orientation during migration
Curr. Biol.
2009
, vol. 
19
 (pg. 
1065
-
1074
)
29
Horgan
C.P.
Hanscom
S.R.
McCaffrey
M.W.
Dynein LIC1 localizes to the mitotic spindle and midbody and LIC2 localizes to spindle poles during cell division
Cell Biol. Int.
2010
, vol. 
35
 (pg. 
171
-
178
)
30
Horgan
C.P.
Hanscom
S.R.
Jolly
R.S.
Futter
C.E.
McCaffrey
M.W.
Rab11–FIP3 binds dynein light intermediate chain 2 and its overexpression fragments the Golgi complex
Biochem. Biophys. Res. Commun.
2010
, vol. 
394
 (pg. 
387
-
392
)
31
Horgan
C.P.
Hanscom
S.R.
Jolly
R.S.
Futter
C.E.
McCaffrey
M.W.
Rab11–FIP3 links the Rab11 GTPase and cytoplasmic dynein to mediate transport to the endosomal-recycling compartment
J. Cell Sci.
2010
, vol. 
123
 (pg. 
181
-
191
)
32
Gupta
V.
Palmer
K.J.
Spence
P.
Hudson
A.
Stephens
D.J.
Kinesin-1 (uKHC/KIF5B) is required for bidirectional motility of ER exit sites and efficient ER-to-Golgi transport
Traffic
2008
, vol. 
9
 (pg. 
1850
-
1866
)
33
Welte
M.A.
Bidirectional transport: matchmaking for motors
Curr. Biol.
2010
, vol. 
20
 (pg. 
R410
-
R413
)
34
Kural
C.
Kim
H.
Syed
S.
Goshima
G.
Gelfand
V.I.
Selvin
P.R.
Kinesin and dynein move a peroxisome in vivo: a tug-of-war or coordinated movement?
Science
2005
, vol. 
308
 (pg. 
1469
-
1472
)
35
Zerial
M.
McBride
H.
Rab proteins as membrane organizers
Nat. Rev. Mol. Cell Biol.
2001
, vol. 
2
 (pg. 
107
-
117
)
36
van Weering
J.R.
Verkade
P.
Cullen
P.J.
SNX-BAR proteins in phosphoinositide-mediated, tubular-based endosomal sorting
Semin. Cell. Dev. Biol.
2009
, vol. 
21
 (pg. 
371
-
380
)
37
Jordens
I.
Marsman
M.
Kuijl
C.
Neefjes
J.
Rab proteins, connecting transport and vesicle fusion
Traffic
2005
, vol. 
6
 (pg. 
1070
-
1077
)
38
Haft
C.R.
de la Luz Sierra
M.
Barr
V.A.
Haft
D.H.
Taylor
S.I.
Identification of a family of sorting nexin molecules and characterization of their association with receptors
Mol. Cell. Biol.
1998
, vol. 
18
 (pg. 
7278
-
7287
)
39
Carlton
J.
Bujny
M.
Peter
B.J.
Oorschot
V.M.
Rutherford
A.
Mellor
H.
Klumperman
J.
McMahon
H.T.
Cullen
P.J.
Sorting nexin-1 mediates tubular endosome-to-TGN transport through coincidence sensing of high- curvature membranes and 3-phosphoinositides
Curr. Biol.
2004
, vol. 
14
 (pg. 
1791
-
1800
)
40
Traer
C.J.
Rutherford
A.C.
Palmer
K.J.
Wassmer
T.
Oakley
J.
Attar
N.
Carlton
J.G.
Kremerskothen
J.
Stephens
D.J.
Cullen
P.J.
SNX4 coordinates endosomal sorting of TfnR with dynein-mediated transport into the endocytic recycling compartment
Nat. Cell Biol.
2007
, vol. 
9
 (pg. 
1370
-
1380
)
41
Skanland
S.S.
Walchli
S.
Brech
A.
Sandvig
K.
SNX4 in complex with clathrin and dynein: implications for endosome movement
PLoS ONE
2009
, vol. 
4
 pg. 
e5935
 
42
Wassmer
T.
Attar
N.
Harterink
M.
van Weering
J.R.
Traer
C.J.
Oakley
J.
Goud
B.
Stephens
D.J.
Verkade
P.
Korswagen
H.C.
Cullen
P.J.
The retromer coat complex coordinates endosomal sorting and dynein-mediated transport, with carrier recognition by the trans-Golgi network
Dev. Cell
2009
, vol. 
17
 (pg. 
110
-
122
)
43
Puthenveedu
M.A.
Lauffer
B.
Temkin
P.
Vistein
R.
Carlton
P.
Thorn
K.
Taunton
J.
Weiner
O.D.
Parton
R.G.
von Zastrow
M.
Sequence-dependent sorting of recycling proteins by actin-stabilized endosomal microdomains
Cell
2010
, vol. 
143
 (pg. 
761
-
773
)
44
Roux
A.
Uyhazi
K.
Frost
A.
De Camilli
P.
GTP-dependent twisting of dynamin implicates constriction and tension in membrane fission
Nature
2006
, vol. 
441
 (pg. 
528
-
531
)
45
Dyve
A.B.
Bergan
J.
Utskarpen
A.
Sandvig
K.
Sorting nexin 8 regulates endosome-to-Golgi transport
Biochem. Biophys. Res. Commun.
2009
, vol. 
390
 (pg. 
109
-
114
)
46
Mukhopadhyay
A.
Nieves
E.
Che
F.Y.
Wang
J.
Jin
L.
Murray
J.W.
Gordon
K.
Angeletti
R.H.
Wolkoff
A.W.
Proteomic analysis of endocytic vesicles: Rab1a regulates motility of early endocytic vesicles
J. Cell Sci.
2011
, vol. 
124
 (pg. 
765
-
775
)
47
Imamura
T.
Huang
J.
Usui
I.
Satoh
H.
Bever
J.
Olefsky
J.M.
Insulin-induced GLUT4 translocation involves protein kinase Cλ-mediated functional coupling between Rab4 and the motor protein kinesin
Mol. Cell. Biol.
2003
, vol. 
23
 (pg. 
4892
-
4900
)
48
Satoh
D.
Sato
D.
Tsuyama
T.
Saito
M.
Ohkura
H.
Rolls
M.M.
Ishikawa
F.
Uemura
T.
Spatial control of branching within dendritic arbors by dynein-dependent transport of Rab5-endosomes
Nat. Cell Biol.
2008
, vol. 
10
 (pg. 
1164
-
1171
)
49
Rojas
R.
van Vlijmen
T.
Mardones
G.A.
Prabhu
Y.
Rojas
A.L.
Mohammed
S.
Heck
A.J.
Raposo
G.
van der Sluijs
P.
Bonifacino
J.S.
Regulation of retromer recruitment to endosomes by sequential action of Rab5 and Rab7
J. Cell Biol.
2008
, vol. 
183
 (pg. 
513
-
526
)
50
Jordens
I.
Fernandez-Borja
M.
Marsman
M.
Dusseljee
S.
Janssen
L.
Calafat
J.
Janssen
H.
Wubbolts
R.
Neefjes
J.
The Rab7 effector protein RILP controls lysosomal transport by inducing the recruitment of dynein–dynactin motors
Curr. Biol.
2001
, vol. 
11
 (pg. 
1680
-
1685
)