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Curr Opin Cell Biol. Author manuscript; available in PMC 2010 August 1.
Published in final edited form as:
PMCID: PMC2725219

The Exocyst Complex in Polarized Exocytosis


The exocyst is an octameric protein complex, which mediates the tethering of post-Golgi secretory vesicles to the plasma membrane prior to exocytic fusion. The exocyst assembles by side-by-side packing of rod-shaped subunits composed of helical bundles. The targeting of secretory vesicles to the plasma membrane involves direct interactions of the exocyst with PI(4,5)P2. In addition, a number of small GTP-binding proteins interact with components of the exocyst and regulate the assembly, localization, and function of this complex. Here we review the recent advances in the field, focusing on the function of the exocyst in polarized exocytosis.

Polarized exocytosis is essential for a wide range of biological processes such as cell growth, morphogenesis, and cell migration. Exocytosis is accomplished by the fusion of secretory vesicles with the plasma membrane catalyzed by the assembly of the SNARE complex. Prior to membrane fusion, additional proteins mediate the initial interaction between the vesicles and the acceptor membrane, a process known as “vesicle tethering”. Tethering of secretory vesicles to the plasma membrane is thought to be mediated by the exocyst, an evolutionarily conserved octameric protein complex consisting of Sec3, Sec5, Sec6, Sec8, Sec10, Sec15, Exo70, and Exo84 [[1**] and [2**]]. Recent studies from different disciplines have led to significant advance in our understanding of the exocyst in various eukaryotic systems and physiological processes. Here we review the most recent progresses in the field, focusing on the role of the exocyst in exocytosis.

The structure of the exocyst

Understanding the structure of the exocyst may provide important insight into the molecular mechanism of the exocyst function. So far, partial crystal structures of four exocyst components have been solved [3]. These include the near full-length yeast and mouse Exo70 [[4**], [5] and [6]], and the C-terminal domains of Drosophila Sec15 [7], yeast Exo84 [4**], and yeast Sec6 [8**]. While these exocyst components share little sequence homology, they all display rod-like structures composed of two or more consecutively packed helical bundles, with each bundle consisting of three to five α-helices linked by loops. The structural conservation among exocyst components suggests that they evolved from a common ancestor. In addition, several exocyst components have been found to share distant sequence homology with subunits of two other tethering complexes that function at the Golgi apparatus, the conserved oligomeric Golgi (COG) complex and the Golgi-associated retrograde protein (GARP) complex [9]. The crystal structure of the COG subunit COG2 shows a helical bundle structure similar to that of the exocyst components [10]. These findings suggest that the exocyst, the COG and the GARP complexes are structurally related and might have diverged from a common ancestor to mediate vesicle tethering at different membrane trafficking stages.

The structure of individual exocyst components also provides a clue to how the exocyst complex is assembled. For example, Exo70 has an extended rod-shaped structure. Mapping the binding sites of Sec8 and Sec10 on Exo70 indicates that they have an extended interface with Exo70, suggesting that Sec8 and Sec10 themselves also have extended rod-like structures [4**]. Therefore, the assembly of the exocyst complex likely involves the packing of at least some rod-shaped components in a side-to-side fashion. This is consistent with the previous structure study of the mammalian exocyst complex using quick-freeze/deep-etch electron microscopy which demonstrates that the exocyst displays a packed “Y”-shaped structure after fixation [11*]. To date, the subunit organization and the structure of the holo-exocyst complex remain unclear. However, the recent crystal structure data have provided valuable insights to the structure and molecular organization of the exocyst complex.

Polarized localization and activation of the exocyst at the plasma membrane

In order to understand how the exocyst tethers vesicles at the plasma membrane, it is important to elucidate how the exocyst itself is targeted to the plasma membrane. In yeast, although all the exocyst components are localized to the growing end of the daughter cells (“bud tip”), their targeting involves different mechanisms. Sec3 is localized to the bud tip independent of actin cables, along which the vesicles are transported [[12*] and [13**]]. Exo70 polarization seems to be partially actin-dependent [13**]. In contrast, the remaining exocyst components are associated with exocytic vesicles and depend on actin cables for their delivery to sites of exocytosis [[13**], [14] and [15]]. These results led to the hypothesis that Sec3 and Exo70 associate with the plasma membrane and interact with the rest of the exocyst components on the arriving vesicles. The assembly of the exocyst complex may tether the secretory vesicles to the plasma membrane.

What recruits Sec3 and Exo70 to the plasma membrane? Recent studies revealed that both components bind to phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) located at the inner leaflet of the plasma membrane [16**, 17 and 18**]. The exocyst components are no longer associated with the plasma membrane in yeast mutant cells in which the plasma membrane PI(4,5)P2 level was reduced [16**]. Simultaneously disrupting the interaction of PI(4,5)P2 with Sec3 and Exo70 blocks the plasma membrane association of the exocyst and results in severe secretion and growth defects or cell lethality [[16**] and [18**]]. Sec3 interacts with PI(4,5)P2 through a polybasic region at its N-terminal domain [18**]. Exo70 interacts with PI(4,5)P2 through a number of basic residues at its C-terminus [16**]. These basic residues, while sparsely distributed in the primary sequence, are clustered as a positively charged surface patch at the C-terminal end of the folded Exo70 [[4**], [5] and [6]]. Exo70 specifically binds to PI(4,5)P2 and shows little or no interaction with the stereoisomeric PI(3,5)P2 or mono-phosphorylated PI(3)P and PI(4)P, which are distributed to other membrane compartments [16**]. Similar to their yeast counterparts, mammalian Sec3 and Exo70 also interact with PI(4,5)P2 through conserved regions [[17]; Guo lab unpublished data]. Other tethering factors, such as the HOPS complex that functions in yeast homotypic vacuolar fusion, have also been found to interact with phosphoinositides [19]. Phosphoinositides may function to recruit the tethering proteins to specific membrane compartments for vesicle tethering. A model illustrating the membrane association of the exocyst and its interaction with small GTP-binding proteins (see later) is shown in Figure 1.

Figure 1
A model for the function of the exocyst complex in tethering the secretory vesicles to the plasma membrane in yeast

In yeast, PI(4,5)P2 is not restricted to the daughter cell membrane. Therefore there must be additional factors that contribute to the polarized localization of the exocyst. In budding yeast, the exocyst is diffused in several cdc42 and rho1 mutants [[20] and [21]]. Sec3 is a downstream effector of both Cdc42 and Rho1. GTP-bound Rho1 and Cdc42 compete for their binding to the N-terminal region of Sec3 [20], leading to the speculation that they control Sec3 localization at different cell cycle stages or growth conditions. Sec3 with its N-terminus deleted shows synthetic growth defects with other exocyst mutants [[22], [18**] and [23]]. Cdc42 binds to Sec3 at a region adjacent to its PI(4,5)P2-binding motif and controls Sec3 localization in synergy with PI(4,5)P2 [18**]. Interestingly, a chimera in which the N-terminus of Sec3 was replaced by the N-terminus of Gic2, which binds PI(4,5)P2 through a polybasic domain and binds GTP-bound Cdc42 through its CRIB domain, functions as well as the wild-type Sec3 in yeast cells [18**]. Cdc42 and PI(4,5)P2 may regulate the recruitment of Sec3 to the bud tip. They may also be involved in the activation of the exocyst at the bud tip during polarized yeast cell growth (“budding”). The observed polarization of the exocyst may in fact be a result of both physical recruitment and kinetic reinforcement since polarity determinants such as Cdc42 itself rely on a functional secretory pathway [14, 24].

While Sec3 and Exo70 directly associate with the plasma membrane, their stable polarization in cells also depends on the other members of the exocyst complex [15, 22, and 23]. Future studies are needed for a more comprehensive understanding of exocyst polarization.

Communication with the SNAREs

Vesicle tethering precedes fusion. In exocyst mutants, assembly of the SNARE complex is blocked [25]. The exocyst is likely to interact with the SNAREs and regulate SNARE assembly. It was reported that the brain exocyst complex co-immunoprecipitated with syntaxin [2**]. Yeast Sec6 was shown to interact with the t-SNARE Sec9 in vitro and may inhibit Sec9 interaction with the other t-SNARE protein Sso1 [26]. The exocyst was also found to co-immunoprecipitate with Sec1 [27], a Sec1/Munc18 (SM) family protein, which binds to SNAREs and stimulates membrane fusion. The exocyst component Exo84 directly interacts with the yeast lgl homologues Sro7/77 [28], which bind to and activate Sec9 [[29] and [30]]. Sro7/77 is a downstream effector of Sec4, a Rab GTPase that regulates post-Golgi stage of exocytosis [31]. In mammalian cells, Exo70 interacts with the t-SNARE binding protein Snapin [32]. Similar to the exocyst, the majority of tethering complexes in different stages of membrane traffic were shown to interact with t-SNAREs at the corresponding acceptor membranes. For example, the HOPS complex was shown to interact with the SNAREs and promote SNARE-mediated fusion in vitro [33]. It may be a common theme that the tethering factors regulate SNARE assembly through multitude interactions to coordinate vesicle tethering and fusion.

Function of the exocyst in exocytosis and beyond

In yeast, the exocyst mutants exhibit blockages of secretion and show intracellular accumulation of secretory vesicles [34**, 35, 15 and 36*]. In animal cells, the role of the exocyst in exocytosis and cell surface expansion has been demonstrated in a variety of cell types, such as protein targeting in epithelial cells [37** and 38*], dendritic delivery of NMDA receptors at postsynaptic membranes [39], and insulin-induced exocytosis of glucose transporter in adipocytes [40*]. It is worth noting that the exocyst is not required for all types of exocytic events in animal cells. For example, the exocyst does not seem to play a major role during neurotransmitter release at mature synapses, a specialized form of regulated exocytosis [41].

In animal cells, the exocyst components were found at the TGN and the perinuclear recycling endosomes [42*, 43*, 44*, 45 and 38*]. Recycling endosomes mediate the transport of the internalized plasma membrane receptors back to the cell surface and are major sources of cargos destined to the plasma membrane in many types of cells. Loss of exocyst function blocks the recycling of internalized cargos and results in their accumulation in recycling endosomes [43*, 45 and 38*]. Since in animal cells the exocyst is localized to both the plasma membrane and perinuclear membrane compartments, it is possible that different pools of the exocyst function in different vesicular trafficking stages and that disruption of a specific pool of the exocyst leads to defect at the corresponding vesicular trafficking stage [42*].

The exocyst has been implicated in a variety of cellular processes including cytokinesis, cell migration, tumor invasion, and ciliogenesis. Furthermore, the exocyst has been shown to play important roles in a multitude of developmental processes, such as the establishment or remodeling of epithelial polarity, cell fate determination, neural and eye development, and oogenesis. In plants, the exocyst has been implicated in polarized cell growth such as pollen tube growth and hypocotyls elongation. Together, these in vivo studies have revealed various functions of the exocyst at the tissue and organ level. Due to the focus on the basic mechanisms of exocytosis in this review, these important works are not discussed and referenced here.

Regulation of the exocyst by small GTP-binding proteins

Functioning at a step before SNARE-mediated fusion, the exocyst is a target of a number of regulators that spatially and kinetically regulate exocytosis in cells. In particular, several small GTP-binding proteins directly interact with the exocyst. In yeast, Sec15 is a downstream effector of the Rab GTPase Sec4, which regulates the assembly of the exocyst complex [46**]. In higher eukaryotes, Sec15 is a downstream effector of the Rab GTPase Rab11, which regulates vesicle transport to the plasma membrane from recycling endosomes [7, 38*, 45 and 47*]. Several other tethering factors have also been shown to interact with specific Rab GTPases that regulate the corresponding membrane trafficking stages. The regulation of specific tethering proteins by distinct sets of Rab GTPases may be a common mechanism that assures membrane traffic fidelity. In mammalian cells, Sec10 is a downstream effector of the small GTPase Arf6, which promotes the translocation of Sec10 from recycling endosomes to the plasma membrane during cell surface remodeling and spreading [43*].

In budding yeast, Sec3 is a downstream effector of Cdc42 and Rho1 (see above). In addition, Exo70 was shown to interact with the GTP-bound form of Rho3, which is implicated in exocytosis [4**, 48, 49]. However, mutations in Exo70 that disrupt its interaction with Rho3 did not affect exocyst polarization or exocytosis [16** and 50]. It was speculated that in addition to Rho3, other factor(s) interact with Exo70 and regulate its activity [16** and 50]. Studies in yeast demonstrate that the exo70 mutants, unlike other exocyst mutants, are primarily defective in the secretion of a subset of exocytic vesicles [36*]. These vesicles carry cargos such as the endoglucanase Bgl2 that are needed for cell wall remodeling and plasma membrane expansion. In addition, the secretion defect in the exo70 mutants is most prominent at the early stage of asymmetric daughter cell growth. It has been previously reported that a particular mutant allele of Cdc42, cdc42-6, specifically accumulates Bgl2 vesicles in small-budded cells [51*]. The phenotypical similarity between cdc42-6 and the exo70 mutants suggests that Exo70 functions downstream of Cdc42. In mammalian cells, Exo70 interacts with TC10 (a homolog of Cdc42) and this interaction was shown to be important for the fusion, rather than the delivery, of Glut4 vesicles to the plasma membrane in adipocytes in response to insulin [40*]. Consistent with this observation, HeLa cells with Exo70 knocked down by RNAi blocked the fusion of post-Golgi vesicles to the plasma membrane without significant effect on vesicle delivery [17].

A number of papers from different labs have demonstrated that the exocyst components Sec5 and Exo84 are downstream effectors of the small GTPase Ral. Ral regulates exocyst assembly; disruption of the Ral-exocyst interaction by overexpressing the Ral-binding domain of Sec5 inhibited protein targeting to the basolateral domain in polarized epithelial cells and secretion of secretory granules in neuroendocrine cells [52**]. Besides its role in exocytosis, the Ral-exocyst interaction has also been implicated in actin-based membrane protrusion, cytokinesis, and neurite branching.

Overall, the exocyst seems to function as a hub for receiving regulatory information from various signaling pathways for precise spatiotemporal control of exocytosis. Studies of the exocyst and other tethering complexes imply that these tethering complexes not only physically tether the vesicles to the acceptor membrane, but may also regulate the assembly of the SNARE complex for membrane fusion. In addition, the interactions of specific tethering proteins with distinct sets of Rab GTPases and phosphoinositides may be crucial for membrane traffic fidelity and organelle identity.

Future perspectives

Recent decade saw exciting progresses towards our understanding of the exocyst. However, a number of important questions remain unanswered: What are the kinetics of exocyst assembly and disassembly? How are the exocyst components associated with secretory vesicles? While it is thought that the exocyst serves as a vesicle tether, can the tethering step be observed and characterized by microscopy? Is the exocyst just a physical tether or does it also activate the assembly of the SNARE complex? Is the exocyst also involved in the early steps of vesicular trafficking such as vesicle budding and cargo sorting at the donor compartments? Recent studies demonstrate the roles of the exocyst in a number of developmental and physiological processes. Future studies are needed to elucidate how the cellular functions of the exocyst are manifested at the multicellular organismal level. Combined efforts from cell biologists, structural biologists, and developmental biologists will not only elucidate the functions of this fascinating complex, but also help us better understand exocytosis and cell polarity in general.


Due to space limitations and the focus on exocytosis in this review, we were unable to provide a complete survey of the field, especially exciting new topics related to cytokinesis, cell migration, and development. We apologize for any references we may have left out. Research in Wei Guo’s lab is supported by grants from the National Institutes of Health, American Heart Association and the Pew Scholars Program.


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1** TerBush DR, Maurice T, Roth D, Novick P. The Exocyst is a multiprotein complex required for exocytosis in Saccharomyces cerevisiae. EMBO J. 1996;15(23):6483–94. A seminal paper showing the purification of the exocyst and identification of the individual subunit in yeast. [PubMed]
2** Hsu SC, Ting AE, Hazuka CD, Davanger S, Kenny JW, Kee Y, Scheller RH. The mammalian brain rsec6/8 complex. Neuron. 1996;17(6):1209–19. First purification of mammalian exocyst complex from rat brain extract by chromatography. [PubMed]
3. Munson M, Novick P. The exocyst defrocked, a framework of rods revealed. Nat Struct Mol Biol. 2006;13(7):577–81. Review. [PubMed]
4** Dong G, Hutagalung AH, Fu C, Novick P, Reinisch KM. The structures of exocyst subunit Exo70p and the Exo84p C-terminal domains reveal a common motif. Nat Struct Mol Biol. 2005;12(12):1094–100. This paper demonstrates the crystal structure of near full length of yeast Exo70 and the C-terminal domain of yeast Exo84. Exo70 and Exo84CT are principally composed of α-helices that fold into four and two helical bundles, respectively. These helical bundles pack against each other and form rod-shape structures. The authors also show that the C-terminus of Exo70 contains a number of basic residues that cluster into an electropositive surface patch. [PubMed]
5. Hamburger ZA, Hamburger AE, West AP, Jr, Weis WI. Crystal structure of the S. cerevisiae exocyst component Exo70p. J Mol Biol. 2006;356(1):9–21. [PubMed]
6. Moore BA, Robinson HH, Xu Z. The crystal structure of mouse Exo70 reveals unique features of the mammalian exocyst. J Mol Biol. 2007;371(2):410–21. [PMC free article] [PubMed]
7. Wu S, Mehta SQ, Pichaud F, Bellen HJ, Quiocho FA. Sec15 interacts with Rab11 via a novel domain and affects Rab11 localization in vivo. Nat Struct Mol Biol. 2005;12(10):879–85. [PubMed]
8** Sivaram MV, Furgason ML, Brewer DN, Munson M. The structure of the exocyst subunit Sec6p defines a conserved architecture with diverse roles. Nat Struct Mol Biol. 2006;13(6):555–6. The paper shows the crystal structure of the C-terminal domain of Sec6 composed of tandem helical-bundles. Structure comparison between Sec6CT and other exocyst components showed that they all share similar helical-bundles. These observations suggest that the exocyst subunits evolve from a common ancestor and acquire distinct surface features for their specific protein-protein interactions. [PubMed]
9. Whyte JR, Munro S. The Sec34/35 Golgi transport complex is related to the exocyst, defining a family of complexes involved in multiple steps of membrane traffic. Dev Cell. 2001;1(4):527–37. [PubMed]
10. Cavanaugh LF, Chen X, Richardson BC, Ungar D, Pelczer I, Rizo J, Hughson FM. Structural analysis of conserved oligomeric Golgi complex subunit 2. J Biol Chem. 2007;282(32):23418–26. [PubMed]
11* Hsu SC, Hazuka CD, Roth R, Foletti DL, Heuser J, Scheller RH. Subunit composition, protein interactions, and structures of the mammalian brain sec6/8 complex and septin filaments. Neuron. 1998;20(6):1111–22. First structural study of the exocyst by quick-freeze/deep-etch electron microscopy. [PubMed]
12* Finger FP, Hughes TE, Novick P. Sec3p is a spatial landmark for polarized secretion in budding yeast. Cell. 1998;92:559–571. The first comprehensive analysis of an exocyst component in live yeast cells. [PubMed]
13** Boyd C, Hughes T, Pypaert M, Novick P. Vesicles carry most exocyst subunits to exocytic sites marked by the remaining two subunits, Sec3p and Exo70p. J Cell Biol. 2004;167(5):889–901. An elegant fluorescence microscopic study demonstrating that different exocyst components are targeted to the plasma membrane through different mechanisms. [PMC free article] [PubMed]
14. Zajac A, Sun X, Zhang J, Guo W. Cyclical regulation of the exocyst and cell polarity determinants for polarized cell growth. Mol Biol Cell. 2005;16:1500–1512. [PMC free article] [PubMed]
15. Zhang X, Zajac A, Zhang J, Wang P, Li M, Murray J, Terbush D, Guo W. The critical role of Exo84p in the organization and polarized localization of the exocyst complex. J Biol Chem. 2005;280(21):20356–20364. [PubMed]
16** He B, Xi F, Zhang X, Zhang J, Guo W. Exo70 interacts with phospholipids and mediates the targeting of the exocyst to the plasma membrane. EMBO J. 2007;26(18):4053–65. This is the first paper showing that the exocyst interacts with PI(4,5)P2 and is targeted to the plasma membrane through this interaction. The authors report that yeast Exo70 directly interact with PI(4,5)P2 through conserved basic residues located at its C-terminus. Further genetic and cell biological analyses suggest that Exo70 and Sec3 function in concert in targeting the exocyst to the plasma membrane. [PubMed]
17. Liu J, Zuo X, Yue P, Guo W. Phosphatidylinositol 4, 5-bisphosphate mediates the targeting of the exocyst to the plasma membrane for exocytosis in mammalian cells. Mol Biol Cell. 2007;18(11):4483–92. [PMC free article] [PubMed]
18** Zhang X, Orlando K, He B, Xi F, Zhang J, Zajac A, Guo W. Membrane association and functional regulation of Sec3 by phospholipids and Cdc42. J Cell Biol. 2008;180(1):145–58. This paper showed that Sec3 interacts with PI(4,5)P2 and disrupting the Sec3-PI(4,5)P2 or Sec3-Cdc42 interaction affects the actin-independent polarization of Sec3 in yeast. [PMC free article] [PubMed]
19. Stroupe C, Collins KM, Fratti RA, Wickner W. Purification of active HOPS complex reveals its affinities for phosphoinositides and the SNARE Vam7p. EMBO J. 2006;25(8):1579–89. [PubMed]
20. Zhang X, Bi E, Novick P, Du L, Kozminski KG, Lipschutz J, Guo W. Cdc42 interacts with the exocyst and regulates polarized secretion. J Biol Chem. 2001;276(50):46745–46750. [PubMed]
21. Guo W, Tamanoi F, Novick P. Spatial regulation of the exocyst complex by Rho1 GTPase. Nat Cell Biol. 2001;3(4):353–360. [PubMed]
22. Roumanie O, Wu H, Molk JN, Rossi G, Bloom K, Brennwald P. Rho GTPase regulation of exocytosis in yeast is independent of GTP hydrolysis and polarization of the exocyst complex. J Cell Biol. 2005;170(4):583–594. [PMC free article] [PubMed]
23. Songer JA, Munson M. Sec6p anchors the assembled exocyst complex at sites of secretion. Mol Biol Cell. 2009;20(3):973–82. [PMC free article] [PubMed]
24. Wedlich-Soldner R, Altschuler S, Wu L, Li R. Spontaneous cell polarization through actomyosin-based delivery of the Cdc42 GTPase. Science. 2003;299(5610):1231–5. [PubMed]
25. Grote E, Carr CM, Novick PJ. Ordering the final events in yeast exocytosis. J Cell Biol. 2000;151(2):439–52. [PMC free article] [PubMed]
26. Sivaram MV, Saporita JA, Furgason ML, Boettcher AJ, Munson M. Dimerization of the exocyst protein Sec6p and its interaction with the t-SNARE Sec9p. Biochemistry. 2005;44(16):6302–11. [PubMed]
27. Wiederkehr A, De Craene JO, Ferro-Novick S, Novick P. Functional specialization within a vesicle tethering complex: bypass of a subset of exocyst deletion mutants by Sec1p or Sec4p. J Cell Biol. 2004;167(5):875–87. [PMC free article] [PubMed]
28. Zhang X, Wang P, Gangar A, Zhang J, Brennwald P, TerBush D, Guo W. Lethal giant larvae proteins interact with the exocyst complex and are involved in polarized exocytosis. J Cell Biol. 2005;170(2):273–83. [PMC free article] [PubMed]
29. Lehman K, Rossi G, Adamo JE, Brennwald P. Yeast homologues of tomosyn and lethal giant larvae function in exocytosis and are associated with the plasma membrane SNARE, Sec9. J Cell Biol. 1999;146(1):125–40. [PMC free article] [PubMed]
30. Hattendorf DA, Andreeva A, Gangar A, Brennwald PJ, Weis WI. Structure of the yeast polarity protein Sro7 reveals a SNARE regulatory mechanism. Nature. 2007;446(7135):567–71. [PubMed]
31. Grosshans BL, Andreeva A, Gangar A, Niessen S, Yates JR, 3rd, Brennwald P, Novick P. The yeast lgl family member Sro7p is an effector of the secretory Rab GTPase Sec4p. J Cell Biol. 2006;172(1):55–66. [PMC free article] [PubMed]
32. Bao Y, Lopez JA, James DE, Hunziker W. Snapin interacts with the Exo70 subunit of the exocyst and modulates GLUT4 trafficking. J Biol Chem. 2008;283(1):324–31. [PubMed]
33. Mima J, Hickey CM, Xu H, Jun Y, Wickner W. Reconstituted membrane fusion requires regulatory lipids, SNAREs and synergistic SNARE chaperones. EMBO J. 2008;27(15):2031–42. [PubMed]
34** Novick P, Field C, Schekman R. Identification of 23 complementation groups required for post-translational events in the yeast secretory pathway. Cell. 1980;21(1):205–215. A landmark paper reporting the identification of yeast sec mutants (including six of the eight exocyst mutants) that function in the secretory pathway. [PubMed]
35. Guo W, Grant A, Novick P. Exo84p is an exocyst protein essential for secretion. J Biol Chem. 1999;274(33):23558–64. [PubMed]
36* He B, Xi F, Zhang J, TerBush D, Zhang X, Guo W. Exo70p mediates the secretion of specific exocytic vesicles at early stages of cell cycle for polarized cell growth. J Cell Biol. 2007;176(6):771–777. Demonstrated an intimate coupling between exocyst and polarized cell growth in budding yeast. [PMC free article] [PubMed]
37** Grindstaff KK, Yeaman C, Anandasabapathy N, Hsu SC, Rodriguez-Boulan E, Scheller RH, Nelson WJ. Sec6/8 complex is recruited to cell-cell contacts and specifies transport vesicle delivery to the basal-lateral membrane in epithelial cells. Cell. 1998;93(5):731–40. The authors show that the exocyst is recruited from cytosol to the plasma membrane at sites of early cell-cell contact during the formation of polarized epithelial monolayers. In fully polarized cells, the exocyst is enriched at the apical portion of the lateral membrane and is required for protein targeting to the basolateral domain but not the apical domain. [PubMed]
38* Oztan A, Silvis M, Weisz OA, Bradbury NA, Hsu SC, Goldenring JR, Yeaman C, Apodaca G. Exocyst requirement for endocytic traffic directed toward the apical and basolateral poles of polarized MDCK cells. Mol Biol Cell. 2007;18(10):3978–3992. The authors carefully examined the function of the exocyst in different endocytic recycling pathways in polarized epithelial cells. The exocyst components were found to be colocalized with Rab11-positive apical recycling endosomes. Disruption of the exocyst function blocks multiple endocytic recycling pathways, including basolateral recycling, apical recycling, and basolateral-to-apical transcytosis. [PMC free article] [PubMed]
39. Sans N, Prybylowski K, Petralia RS, Chang K, Wang YX, Racca C, Vicini S, Wenthold RJ. NMDA receptor trafficking through an interaction between PDZ proteins and the exocyst complex. Nat Cell Biol. 2003;5(6):520–30. [PubMed]
40* Inoue M, Chang L, Hwang J, Chiang SH, Saltiel AR. The exocyst complex is required for targeting of Glut4 to the plasma membrane by insulin. Nature. 2003;422:629–33. This paper shows that Exo70 is a downstream effector of TC10, which promotes the cytoplasm to plasma membrane translocation of Exo70 in adipocytes in response to activation. [PubMed]
41. Murthy M, Garza D, Scheller RH, Schwarz TL. Mutations in the exocyst component Sec5 disrupt neuronal membrane traffic, but neurotransmitter release persists. Neuron. 2003;37(3):433–47. [PubMed]
42* Yeaman C, Grindstaff KK, Wright JR, Nelson WJ. Sec6/8 complexes on trans-Golgi network and plasma membrane regulate late stages of exocytosis in mammalian cells. J Cell Biol. 2001;155(4):593–604. A comprehensive study of exocyst localization and function at the TGN and the plasma membrane. [PMC free article] [PubMed]
43* Prigent M, Dubois T, Raposo G, Derrien V, Tenza D, Rosse C, Camonis J, Chavrier P. ARF6 controls post-endocytic recycling through its downstream exocyst complex effector. J Cell Biol. 2003;163(5):1111–21. The authors demonstrate that the exocyst is localized to the recycling endosomes and involved in recycling of an endocytosed cargo transferrin. In addition, Sec10 has been found to be a downstream effector of Arf6, which promotes Sec10 localize to plasma membrane ruffles upon activation. [PMC free article] [PubMed]
44* Fölsch H, Pypaert M, Maday S, Pelletier L, Mellman I. The AP-1A and AP-1B clathrin adaptor complexes define biochemically and functionally distinct membrane domains. J Cell Biol. 2003;163(2):351–62. This paper shows that in epithelial cells expressing AP-1B, the clathrin adaptor protein specifically expressed in epithelial cells and mediating the trafficking of proteins to the basolateral membrane, promotes the recruitment of the exocyst to the recycling endosomes. [PMC free article] [PubMed]
45. Zhang XM, Ellis S, Sriratana A, Mitchell CA, Rowe T. Sec15 is an effector for the Rab11 GTPase in mammalian cells. J Biol Chem. 2004;279(41):43027–34. [PubMed]
46** Guo W, Roth D, Walch-Solimena C, Novick P. The exocyst is an effecter for Sec4p, targeting secretory vesicles to sites of exocytosis. EMBO J. 1999;18:1071–1080. This is the first paper showing that the exocyst is a downstream effector of the Ras family of small GTPase. The authors demonstrate that yeast Sec15 directly interacts with GTP-bound form of Rab GTPase Sec4 but not other Rabs; mutations in Sec4 inhibited exocyst assembly. This study suggests a mechanism by which the Rab GTPases controls specificity of different vesicular trafficking events by regulating specific downstream vesicle tethering factors. [PubMed]
47* Langevin J, Morgan MJ, Sibarita JB, Aresta S, Murthy M, Schwarz T, Camonis J, Bellaiche Y. Drosophila exocyst components Sec5, Sec6, and Sec15 regulate DE-Cadherin trafficking from recycling endosomes to the plasma membrane. Dev Cell. 2005;9(3):355–76. This paper shows that loss of function of Sec5, Sec6, or Sec15 in Drosophila epithelial cells inhibits recycling of E-cadherin to the plasma membrane and results in its accumulation in enlarged Rab11-positive recycling endosomes. [PubMed]
48. Adamo JE, Rossi G, Brennwald P. The Rho GTPase Rho3 has a direct role in exocytosis that is distinct from its role in actin polarity. Mol Biol Cell. 1999;10:4121–4133. [PMC free article] [PubMed]
49. Robinson NG, Guo L, Imai J, Toh EA, Matsui Y, Tamanoi F. Rho3 of Saccharomyces cerevisiae, which regulates the actin cytoskeleton and exocytosis, is a GTPase which interacts with Myo2 and Exo70. Mol Cell Biol. 1999;19(5):3580–3587. [PMC free article] [PubMed]
50. Hutagalung AH, Coleman J, Pypaert M, Novick PJ. An internal domain of Exo70p is required for actin-independent localization and mediates assembly of specific exocyst components. Mol Biol Cell. 2009;20(1):153–63. [PMC free article] [PubMed]
51* Adamo JE, Moskow JJ, Gladfelter AS, Viterbo D, Lew DJ, Brennwald PJ. Yeast Cdc42 functions at a late step in exocytosis, specifically during polarized growth of the emerging bud. J Cell Biol. 2001;155(4):581–592. Demonstrated a role of Cdc42 in kinetic regulation of exocytosis during yeast budding. [PMC free article] [PubMed]
52** Moskalenko S, Henry DO, Rosse C, Mirey G, Camonis JH, White MA. The exocyst is a Ral effector complex. Nat Cell Biol. 2002;4(1):66–72. Together with other labs, demonstrated that the exocyst is a direct downstream effector of Ral in mammalian cells. [PubMed]