title: A Rab10:RalA G protein cascade regulates insulin-stimulated glucose uptake in adipocytes.
abstract: Insulin-stimulated glucose uptake in fat and muscle is mediated by the major facilitative glucose transporter Glut4. Insulin controls the trafficking of Glut4 to the plasma membrane via regulation of a series of small G proteins, including RalA and Rab10. We demonstrate here that Rab10 is a bona fide target of the GTPase-activating protein AS160, which is inhibited after phosphorylation by the protein kinase Akt. Once activated, Rab10 can increase the GTP binding of RalA by recruiting the Ral guanyl nucleotide exchange factor, Rlf/Rgl2. Rab10 and RalA reside in the same pool of Glut4-storage vesicles in untreated cells, and, together with Rlf, they ensure maximal glucose transport. Overexpression of membrane-tethered Rlf compensates for the loss of Rab10 in Glut4 translocation, suggesting that Rab10 recruits Rlf to membrane compartments for RalA activation and that RalA is downstream of Rab10. Together these studies identify a new G protein cascade in the regulation of insulin-stimulated Glut4 trafficking and glucose uptake.
authors.affiliation: Life Sciences Institute, University of Michigan Medical School, Ann Arbor, MI 48109.
authors.forename: Sheelarani
authors.initials: S
authors.lastname: Karunanithi
authors.affiliation: Life Sciences Institute, University of Michigan Medical School, Ann Arbor, MI 48109 Departments of Internal Medicine and Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109.
authors.forename: Tingting
authors.initials: T
authors.lastname: Xiong
authors.affiliation: Life Sciences Institute, University of Michigan Medical School, Ann Arbor, MI 48109 Departments of Internal Medicine and Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109.
authors.forename: Maeran
authors.initials: M
authors.lastname: Uhm
authors.affiliation: Life Sciences Institute, University of Michigan Medical School, Ann Arbor, MI 48109.
authors.forename: Dara
authors.initials: D
authors.lastname: Leto
authors.affiliation: Life Sciences Institute, University of Michigan Medical School, Ann Arbor, MI 48109.
authors.forename: Jingxia
authors.initials: J
authors.lastname: Sun
authors.affiliation: Life Sciences Institute, University of Michigan Medical School, Ann Arbor, MI 48109 Departments of Internal Medicine and Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109.
authors.forename: Xiao-Wei
authors.initials: XW
authors.lastname: Chen
authors.affiliation: Life Sciences Institute, University of Michigan Medical School, Ann Arbor, MI 48109 Departments of Internal Medicine and Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109 saltiel@umich.edu.
authors.forename: Alan R
authors.initials: AR
authors.lastname: Saltiel
mesh_terms: D016475:3T3 Cells; D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D004789:Enzyme Activation; D020690:GTPase-Activating Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors; D006160:Guanosine Triphosphate / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D051379:Mice; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000819:agonists / Q000378:metabolism*; D020725:ral GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D020690:GTPase-Activating Proteins; D051275:Glucose Transporter Type 4; D020662:Guanine Nucleotide Exchange Factors; D007328:Insulin; C102739:RGL2 protein, human; D034741:RNA, Small Interfering; C490805:Rgl2 protein, mouse; C495692:SLC2A4 protein, human; C518767:TBC1D4 protein, human; D014157:Transcription Factors; D006160:Guanosine Triphosphate; D051057:Proto-Oncogene Proteins c-akt; C492198:RALA protein, human; C538901:Rab10 protein, human; D020691:rab GTP-Binding Proteins; D020725:ral GTP-Binding Proteins; D005947:Glucose
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