Gapex-5, a Rab31 Guanine Nucleotide Exchange Factor that Regulates Glut4 Trafficking in Adipocytes

Lodhi, Irfan J.; Chiang, Shian Huey; Chang, Louise; Vollenweider, Daniel; Watson, Robert; Inoue, Mayumi; Pessin, Jeffrey E.; Saltiel, Alan R.

doi:10.1016/j.cmet.2006.12.006

Cited by 94 publications

(109 citation statements)

References 59 publications

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“…The docking of GLUT4 vesicles with the plasma membrane appears to require the Exocyst complex that is formed from the assembly of 8 distinct proteins [29][30][31][32]. In the case of GLUT4, the Exo70, Sec6 and Sec8 protein component of this complex redistribute to the plasma membrane in response to insulin [29] These events are triggered by the insulin activation of a small GTP binding protein TC10 that recruits Exo70 with Sec6 and Sec8 to lipid raft microdomains in the plasma membrane [33,34]. Moreover, Sec8 associates with the PDZ domain of SAP97 a MAGUK (membrane-associated guanylate kinase) family member that is recruited along with Sec8 [33].…”

Section: Glut4 Vesicle Docking and Plasma Membrane Fusionmentioning

confidence: 99%

“…Expression of a dominant-interfering CIP4/2 mutant inhibited insulin-stimulated GLUT4 translocation. Further studies using CIP4 as bait, identified Gapex-5, a RasGAP and VPS9 domain-containing protein that functions as a guanine nucleotide exchange factor (GEF) for Rab31, a Rab5 subfamily GTPase that involved in trans-Golgi network (TGN)-to-endosome trafficking [34]. Insulin recruited the CIP4/Gapex-5 complex to the plasma membrane, thereby decreasing Rab31 activity.…”

Section: Insulin Signaling Leading To Glut4 Translocationmentioning

confidence: 99%

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

Hou

Pessin

2007

Current Opinion in Cell Biology

130

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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Section: Glut4 Vesicle Docking and Plasma Membrane Fusionmentioning

confidence: 99%

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

130

116

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“…Gapvd1, is an activator of the early endosome regulator protein Rab. It regulates vesicular trafficking processes such as endocytosis of activated transmembrane proteins and exocytosis of GLUT4 vesicles (Hunker et al, 2006;Lodhi et al, 2007). Recent studies have shown that it can regulate EGFR endocytosis and degradation independently of Rab5 function (Su et al, 2007).…”

Section: Vav2 Knockdown Affects Egfr Degradationmentioning

confidence: 99%

VAV2 regulates epidermal growth factor receptor endocytosis and degradation

et al. 2010

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Vav proteins are guanine nucleotide exchange factors for Rho GTPases that regulate cell adhesion, motility, spreading and proliferation in response to growth factor signalling. In this work, we show that Vav2 expression delayed epidermal growth factor receptor (EGFR) internalization and degradation, and enhanced EGFR, ERK and Akt phosphorylations. This effect of Vav2 on EGFR degradation is dependent on its guanine nucleotide exchange function. Knockdown of Vav2 in HeLa cells enhanced EGFR degradation and reduced cell proliferation. epidermal growth factor stimulation led to colocalization of Vav2 with EGFR and Rab5 in endosomes. We further show that the effect of Vav2 on EGFR stability is modulated by its interaction with two endosome-associated proteins and require RhoA function. Thus, in this work, we report for the first time that Vav2 can regulate growth factors receptor signalling by slowing receptor internalization and degradation through its interaction with endosome-associated proteins.

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“…A number of observations have accumulated that describe the possible linkages between insulin receptor tyrosine kinase-derived signaling components and heterotrimetic G-proteins (19). G-proteins participate in insulin-stimulated translocation of glucose transporter GLUT4 in 3T3-L1 adipocytes (20,21). In addition, Ptx can alter the action of insulin (22).…”

Section: Discussionmentioning

confidence: 99%