Specialized Sorting of GLUT4 and Its Recruitment to the Cell Surface Are Independently Regulated by Distinct Rabs

Overview

Journal Mol Biol Cell

Specialties Cell Biology
Molecular Biology

Date 2013 Jun 28

PMID 23804653

Citations 35

Authors

L Amanda Sadacca

Joanne Bruno

Jennifer Wen

Wenyong Xiong

Timothy E McGraw

Affiliations

Soon will be listed here.

Abstract

Adipocyte glucose uptake in response to insulin is essential for physiological glucose homeostasis: stimulation of adipocytes with insulin results in insertion of the glucose transporter GLUT4 into the plasma membrane and subsequent glucose uptake. Here we establish that RAB10 and RAB14 are key regulators of GLUT4 trafficking that function at independent, sequential steps of GLUT4 translocation. RAB14 functions upstream of RAB10 in the sorting of GLUT4 to the specialized transport vesicles that ferry GLUT4 to the plasma membrane. RAB10 and its GTPase-activating protein (GAP) AS160 comprise the principal signaling module downstream of insulin receptor activation that regulates the accumulation of GLUT4 transport vesicles at the plasma membrane. Although both RAB10 and RAB14 are regulated by the GAP activity of AS160 in vitro, only RAB10 is under the control of AS160 in vivo. Insulin regulation of the pool of RAB10 required for GLUT4 translocation occurs through regulation of AS160, since activation of RAB10 by DENND4C, its GTP exchange factor, does not require insulin stimulation.

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References

Brandie F, Aran V, Verma A, McNew J, Bryant N, Gould G . Negative regulation of syntaxin4/SNAP-23/VAMP2-mediated membrane fusion by Munc18c in vitro. PLoS One. 2009; 3(12):e4074. PMC: 2605266. DOI: 10.1371/journal.pone.0004074. View

Chen X, Leto D, Xiong T, Yu G, Cheng A, Decker S . A Ral GAP complex links PI 3-kinase/Akt signaling to RalA activation in insulin action. Mol Biol Cell. 2010; 22(1):141-52. PMC: 3016972. DOI: 10.1091/mbc.E10-08-0665. View

Dugani C, Randhawa V, Cheng A, Patel N, Klip A . Selective regulation of the perinuclear distribution of glucose transporter 4 (GLUT4) by insulin signals in muscle cells. Eur J Cell Biol. 2008; 87(6):337-51. DOI: 10.1016/j.ejcb.2008.02.009. View

Oh E, Thurmond D . Munc18c depletion selectively impairs the sustained phase of insulin release. Diabetes. 2009; 58(5):1165-74. PMC: 2671048. DOI: 10.2337/db08-1059. View

Chen X, Inoue M, Hsu S, Saltiel A . RalA-exocyst-dependent recycling endosome trafficking is required for the completion of cytokinesis. J Biol Chem. 2006; 281(50):38609-16. DOI: 10.1074/jbc.M512847200. View

Ishikura S, Klip A . Muscle cells engage Rab8A and myosin Vb in insulin-dependent GLUT4 translocation. Am J Physiol Cell Physiol. 2008; 295(4):C1016-25. DOI: 10.1152/ajpcell.00277.2008. View

Sano H, Roach W, Peck G, Fukuda M, Lienhard G . Rab10 in insulin-stimulated GLUT4 translocation. Biochem J. 2007; 411(1):89-95. DOI: 10.1042/BJ20071318. View

Sun Y, Bilan P, Liu Z, Klip A . Rab8A and Rab13 are activated by insulin and regulate GLUT4 translocation in muscle cells. Proc Natl Acad Sci U S A. 2010; 107(46):19909-14. PMC: 2993354. DOI: 10.1073/pnas.1009523107. View

Miinea C, Sano H, Kane S, Sano E, Fukuda M, Peranen J . AS160, the Akt substrate regulating GLUT4 translocation, has a functional Rab GTPase-activating protein domain. Biochem J. 2005; 391(Pt 1):87-93. PMC: 1237142. DOI: 10.1042/BJ20050887. View

10.

Lizunov V, Lisinski I, Stenkula K, Zimmerberg J, Cushman S . Insulin regulates fusion of GLUT4 vesicles independent of Exo70-mediated tethering. J Biol Chem. 2009; 284(12):7914-9. PMC: 2658084. DOI: 10.1074/jbc.M806460200. View

11.

Aran V, Bryant N, Gould G . Tyrosine phosphorylation of Munc18c on residue 521 abrogates binding to Syntaxin 4. BMC Biochem. 2011; 12:19. PMC: 3103433. DOI: 10.1186/1471-2091-12-19. View

12.

Itoh T, Satoh M, Kanno E, Fukuda M . Screening for target Rabs of TBC (Tre-2/Bub2/Cdc16) domain-containing proteins based on their Rab-binding activity. Genes Cells. 2006; 11(9):1023-37. DOI: 10.1111/j.1365-2443.2006.00997.x. View

13.

Sano H, Kane S, Sano E, Miinea C, Asara J, Lane W . Insulin-stimulated phosphorylation of a Rab GTPase-activating protein regulates GLUT4 translocation. J Biol Chem. 2003; 278(17):14599-602. DOI: 10.1074/jbc.C300063200. View

14.

Lampson M, Racz A, Cushman S, McGraw T . Demonstration of insulin-responsive trafficking of GLUT4 and vpTR in fibroblasts. J Cell Sci. 2000; 113 ( Pt 22):4065-76. DOI: 10.1242/jcs.113.22.4065. View

15.

Kitt K, Hernandez-Deviez D, Ballantyne S, Spiliotis E, Casanova J, Wilson J . Rab14 regulates apical targeting in polarized epithelial cells. Traffic. 2008; 9(7):1218-31. PMC: 2773667. DOI: 10.1111/j.1600-0854.2008.00752.x. View

16.

Dugani C, Klip A . Glucose transporter 4: cycling, compartments and controversies. EMBO Rep. 2005; 6(12):1137-42. PMC: 1369215. DOI: 10.1038/sj.embor.7400584. View

17.

Blot V, McGraw T . Use of quantitative immunofluorescence microscopy to study intracellular trafficking: studies of the GLUT4 glucose transporter. Methods Mol Biol. 2008; 457:347-66. DOI: 10.1007/978-1-59745-261-8_26. View

18.

Gonzalez E, McGraw T . Insulin-modulated Akt subcellular localization determines Akt isoform-specific signaling. Proc Natl Acad Sci U S A. 2009; 106(17):7004-9. PMC: 2678468. DOI: 10.1073/pnas.0901933106. View

19.

Eguez L, Lee A, Chavez J, Miinea C, Kane S, Lienhard G . Full intracellular retention of GLUT4 requires AS160 Rab GTPase activating protein. Cell Metab. 2005; 2(4):263-72. DOI: 10.1016/j.cmet.2005.09.005. View

20.

DAndrea-Merrins M, Chang L, Lam A, Ernst S, Stuenkel E . Munc18c interaction with syntaxin 4 monomers and SNARE complex intermediates in GLUT4 vesicle trafficking. J Biol Chem. 2007; 282(22):16553-66. DOI: 10.1074/jbc.M610818200. View