A Rab10:RalA G protein cascade regulates insulin-stimulated glucose uptake in adipocytes.
Bottom Line: Once activated, Rab10 can increase the GTP binding of RalA by recruiting the Ral guanyl nucleotide exchange factor, Rlf/Rgl2.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.
Affiliation: Life Sciences Institute, University of Michigan Medical School, Ann Arbor, MI 48109.Show MeSH
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Mentions: We performed subcellular fractionation of 3T3-L1 adipocytes to assess the insulin-dependent changes in the cellular localization of RalA and Rab10. As expected, Glut4, IRAP, and RalA were enriched in the plasma membrane fractions upon insulin stimulation, with a concurrent loss of these proteins in the low-density microsome (LDM) fractions. Of interest, Rab10 localization mirrored that of RalA (Figure 7A).
Affiliation: Life Sciences Institute, University of Michigan Medical School, Ann Arbor, MI 48109.