title: Elmo2 Is a Regulator of Insulin-dependent Glut4 Membrane Translocation.
abstract: Elmo2, a member of the Elmo protein family, has been implicated in the regulation of Rac1 and Akt activation. Recently, we found that Elmo2 specifically interacts with ClipR-59. Because Akt and Rac1 have been implicated in insulin dependent Glut4 membrane translocation, we hypothesize here that Elmo2 may play a role in insulin-dependent Glut4 membrane translocation. Accordingly, we found that overexpression of Elmo2 enhanced, whereas its knockdown suppressed, insulin-dependent Glut4 membrane translocation in both 3T3-L1 adipocytes and L6 skeletal muscle cells. We also examined whether Elmo2 contributes to the insulin-mediated activation of Rac1 and Akt. We found that Elmo2 is required for insulin-induced Rac1 GTP loading, but not AKT activation, in L6 cells induced by insulin. Instead, Elmo2 is required to promote the insulin-induced membrane association of Akt. Together, our studies demonstrate that Elmo2 is a new regulator of insulin-dependent Glut4 membrane translocation through modulating Rac1 activity and Akt membrane compartmentalization.
authors.affiliation: From the Molecular Oncology Research Institute, Tufts Medical Center, Boston, Massachusetts 02111 and.
authors.forename: Yingmin
authors.initials: Y
authors.lastname: Sun
authors.affiliation: the Institut de Recherches Cliniques de Montréal, Université de Montréal, Montréal, Québec H2W 1R7, Canada.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Côté
authors.affiliation: From the Molecular Oncology Research Institute, Tufts Medical Center, Boston, Massachusetts 02111 and kdu@tuftsmedicalcenter.org.
authors.forename: Keyong
authors.identifier: 0000-0002-0284-3576
authors.initials: K
authors.lastname: Du
mesh_terms: D041721:3T3-L1 Cells; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism*; D002522:Chlorocebus aethiops; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; C486678:ELMO2 protein, human; C544335:Elmo2 protein, mouse; D051275:Glucose Transporter Type 4; D007328:Insulin; D009479:Neuropeptides; C107953:RAC1 protein, human; C484602:Rac1 protein, mouse; C495692:SLC2A4 protein, human; C495693:Slc2a4 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D020830:rac1 GTP-Binding Protein
keywords: Akt PKB; Rac (Rac GTPase); adipocyte; glucose transporter type 4 (GLUT4); trafficking