The exocyst complex is required for targeting of Glut4 to the plasma membrane by insulin

Inoue, Mayumi; Chang, Louise; Hwang, Joseph; Chiang, Shian-Huey; Saltiel, Alan R.

doi:10.1038/nature01533

Cited by 325 publications

(396 citation statements)

References 31 publications

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“…Roles for the exocyst in insulin secretion and septins in glucosestimulated growth-hormone release have been reported previously (Inoue et al, 2003;Beites et al, 1999), and the data presented here further indicate that IQGAP1 associates with these protein complexes to regulate their effects on secretion in cooperation with CDC42-GTPase (Figs 1 and 9). This agrees with the finding that stable expression of CDC42, while enhancing mastoparanactivated CDC42 insulin secretion, inhibited glucose-stimulated secretion (Fig.…”

Section: Involvement Of Iqgap1 In Physiological Secretionsupporting

confidence: 80%

“…Whereas the yeast exocyst communicates with several members of the Rho subfamily of small GTPases, including Cdc42p (Lipschutz and Mostov, 2002;Novick and Guo, 2002), in mammals, only RAL (RALA) and TC10 (RHOQ) GTPases have been shown to bind the exocyst (Inoue et al, 2003), and no link has been reported with CDC42. Recently, genetic and biochemical evidence have shown that both yeast and mammalian exocysts communicate with the ER-translocon via an interaction with the Sec61␤ subunit (Lipschutz et al, 2003;Toikkanen et al, 2003), suggesting a role in protein synthesis/translocation events.…”

Section: Introductionmentioning

confidence: 99%

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A dual role for IQGAP1 in regulating exocytosis

Rittmeyer

Daniel

Hsu

et al. 2008

Journal of Cell Science

173

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Polarized secretion is a tightly regulated event generated by conserved, asymmetrically localized multiprotein complexes, and the mechanism(s) underlying its temporal and spatial regulation are only beginning to emerge. Although yeast Iqg1p has been identified as a positional marker linking polarity and exocytosis cues, studies on its mammalian counterpart, IQGAP1, have focused on its role in organizing cytoskeletal architecture, for which the underlying mechanism is unclear. Here, we report that IQGAP1 associates and co-localizes with the exocyst-septin complex, and influences the localization of the exocyst and the organization of septin. We further show that activation of CDC42 GTPase abolishes this association and inhibits secretion in pancreatic β-cells. Whereas the N-terminus of IQGAP1 binds the exocyst-septin complex, enhances secretion and abrogates the inhibition caused by CDC42 or the depletion of IQGAP1, the C-terminus, which binds CDC42, inhibits secretion. Pulse-chase experiments indicate that IQGAP1 influences protein-synthesis rates, thus regulating exocytosis. We propose and discuss a model in which IQGAP1 serves as a conformational switch to regulate exocytosis.

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Section: Involvement Of Iqgap1 In Physiological Secretionsupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

A dual role for IQGAP1 in regulating exocytosis

Rittmeyer

Daniel

Hsu

et al. 2008

Journal of Cell Science

173

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“…Moreover, Sec8 associates with the PDZ domain of SAP97 a MAGUK (membrane-associated guanylate kinase) family member that is recruited along with Sec8 [33]. Interestingly, expression of a dominant-interfering Exo70 protein or siRNA-mediated knockdowns did not prevent GLUT4 vesicle trafficking to the plasma membrane but did inhibit GLUT4 plasma membrane fusion whereas over expression of Sec6 and Sec8 enhanced GLUT4 translocation to the plasma membrane [33,35]. Although these data indicate that the Exocyst complex plays an important role in the insulin-regulated plasma membrane docking/tethering of GLUT4 vesicles, it is well established the physiologic minimal fusion machinery is dependent upon the assembly of the SNARE complex [36][37][38] SNARE proteins can be generally classified as v-SNAREs (or R-SNAREs) that possess a single coil-coiled domain and a transmembrane domain that are localized in vesicle compartment [39][40][41][42].…”

Section: Glut4 Vesicle Docking and Plasma Membrane Fusionmentioning

confidence: 99%

“…In this case, Cbl phosphorylation has been suggested to provide a pathway for the activation of a small GTP binding protein TC10 that is localized to lipid raft microdomains [86]. Using a constitutively active TC10 protein as bait, several interacting partners were identified including Exo70, as previously described, and CIP4/2 [35,87]. CIP4/2 (Cdc42-interacting protein 4/2) is a modular domain protein containing an FCH domain, which has been recently recognized as part of a larger structural domain called EFC or F-BAR.…”

Section: Insulin Signaling Leading To Glut4 Translocationmentioning

confidence: 99%

Ins (endocytosis) and outs (exocytosis) of GLUT4 trafficking

Hou

Pessin

2007

Current Opinion in Cell Biology

132

116

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SummaryGlucose transporter 4 (GLUT4) is the major insulin regulated glucose transporter expressed mainly in muscle and adipose tissue. GLUT4 is stored in a poorly characterized intracellular vesicular compartment and translocates to the cell surface in response to insulin stimulation resulting in increase glucose uptake. This process is essential for the maintenance of normal glucose homeostasis and involves a complex interplay of trafficking events and intracellular signaling cascades. Recent studies have identified sortilin as an essential element for the formation of GLUT4 storage vesicles during adipogenesis and GGA (Golgi-localized γ-ear-containing Arf-binding protein) as a key coat adaptor for the entry of newly synthesized GLUT4 into the specialized compartment. Insulinstimulated GLUT4 translocation from this compartment to the plasma membrane appears to require the Akt/protein kinase B substrate, termed AS160 (Akt Substrate of 160 kDa). In addition, the VPS9 domain-containing protein Gapex-5 in complex with CIP4 appears to function as a Rab31 guanylnucleotide exchange factor that is necessary for insulin-stimulated GLUT4 translocation. Here we attempt to summaries recent advances in GLUT4 vesicle biogenesis, intracellular trafficking and membrane fusion.

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“…As shown in Figure 4 and Table 1, the interaction between exo70-1 and 5% PI(4,5)P 2 was almost abolished, indicating that K632 and K635 are critical residues for the binding of Exo70 to PI(4,5)P 2 . Interestingly, the binding of exo70-1 for PS was only partially affected, suggesting that these two residues confer certain degree of specificity for PI(4,5)P 2 .It was previously shown that Exo70 interacts with the constitutively activated form of TC10 (Q67L; Inoue et al, 2003). We then tested whether mutations in exo70-1 affect this interaction.…”

mentioning

confidence: 99%

Phosphatidylinositol 4,5-Bisphosphate Mediates the Targeting of the Exocyst to the Plasma Membrane for Exocytosis in Mammalian Cells

Liu

Zuo

Peng

et al. 2007

MBoC

196

248

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The exocyst is an evolutionarily conserved octameric protein complex that tethers post-Golgi secretory vesicles at the plasma membrane for exocytosis. To elucidate the mechanism of vesicle tethering, it is important to understand how the exocyst physically associates with the plasma membrane (PM). In this study, we report that the mammalian exocyst subunit Exo70 associates with the PM through its direct interaction with phosphatidylinositol 4,5-bisphosphate (PI(4,5)P 2 ). Furthermore, we have identified key conserved residues at the C-terminus of Exo70 that are crucial for the interaction of Exo70 with PI(4,5)P 2 . Disrupting Exo70-PI(4,5)P 2 interaction abolished the membrane association of Exo70. We have also found that wild-type Exo70 but not the PI(4,5)P 2 -binding-deficient Exo70 mutant is capable of recruiting other exocyst components to the PM. Using the ts045 vesicular stomatitis virus glycoprotein trafficking assay, we demonstrate that Exo70-PI(4,5)P 2 interaction is critical for the docking and fusion of post-Golgi secretory vesicles, but not for their transport to the PM. INTRODUCTIONExocytosis is important for a variety of cellular functions, ranging from the release of hormones to the incorporation of membrane proteins for cell growth and morphogenesis. The late stage of exocytosis is a multistep process that includes directional transport, tethering, docking, and fusion of postGolgi secretory vesicles with the plasma membrane (PM). The tethering step, defined as the initial contact of secretory vesicles with the PM before SNARE-mediated docking and fusion (Pfeffer, 1999;Guo et al., 2000;Waters and Hughson, 2000;Whyte and Munro, 2002), is mediated by the exocyst, an evolutionarily conserved octameric complex composed of Sec3, Sec5, Sec6, Sec8, Sec10, Sec15, Exo70, and Exo84 (for review, see Guo et al., 2000;Hsu et al., 2004;Munson and Novick, 2006;Wang and Hsu, 2006). In budding yeast, the exocyst components localize to the growing end of the daughter cell ("bud"), where active exocytosis and membrane addition take place (TerBush and Novick, 1995;Finger et al., 1998, Guo et al., 1999. This localization pattern contrasts that of the membrane fusion machine, the t-SNAREs, which are evenly distributed along both the mother and daughter cell membrane (Brennwald et al., 1994). In mammalian cells, the exocyst components were found in the cytosol, recycling endosomes and trans-Golgi network Fö lsch et al., 2003;Ang et al., 2004;Langevin et al., 2005). However, they are recruited to the PM during a number of cellular processes. For example, in epithelial cells, the exocyst is recruited to the adherens junction region upon cell-cell contact, where it mediates protein and membrane addition at the basolateral domain (Grindstaff et al., 1998;Yeaman et al., 2001); in developing neurons, the exocyst is localized to the growing neurites, where it mediates membrane expansion (Hazuka et al., 1999;Vega and Hsu, 2001); during cell migration, the exocyst is recruited to the leading edges of the PM (Rosse et al., 2006;...

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The exocyst complex is required for targeting of Glut4 to the plasma membrane by insulin

Cited by 325 publications

References 31 publications

A dual role for IQGAP1 in regulating exocytosis

A dual role for IQGAP1 in regulating exocytosis

Ins (endocytosis) and outs (exocytosis) of GLUT4 trafficking

Phosphatidylinositol 4,5-Bisphosphate Mediates the Targeting of the Exocyst to the Plasma Membrane for Exocytosis in Mammalian Cells

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