title: SEC16A is a RAB10 effector required for insulin-stimulated GLUT4 trafficking in adipocytes.
abstract: RAB10 is a regulator of insulin-stimulated translocation of the GLUT4 glucose transporter to the plasma membrane (PM) of adipocytes, which is essential for whole-body glucose homeostasis. We establish SEC16A as a novel RAB10 effector in this process. Colocalization of SEC16A with RAB10 is augmented by insulin stimulation, and SEC16A knockdown attenuates insulin-induced GLUT4 translocation, phenocopying RAB10 knockdown. We show that SEC16A and RAB10 promote insulin-stimulated mobilization of GLUT4 from a perinuclear recycling endosome/TGN compartment. We propose RAB10-SEC16A functions to accelerate formation of the vesicles that ferry GLUT4 to the PM during insulin stimulation. Because GLUT4 continually cycles between the PM and intracellular compartments, the maintenance of elevated cell-surface GLUT4 in the presence of insulin requires accelerated biogenesis of the specialized GLUT4 transport vesicles. The function of SEC16A in GLUT4 trafficking is independent of its previously characterized activity in ER exit site formation and therefore independent of canonical COPII-coated vesicle function. However, our data support a role for SEC23A, but not the other COPII components SEC13, SEC23B, and SEC31, in the insulin stimulation of GLUT4 trafficking, suggesting that vesicles derived from subcomplexes of COPII coat proteins have a role in the specialized trafficking of GLUT4.
authors.affiliation: Department of Biochemistry, Weill Cornell Medical College, New York, NY 10065 Weill Cornell/Rockefeller/Sloan Kettering Tri-Institutional MD-PhD Program, New York, NY 10065.
authors.forename: Joanne
authors.initials: J
authors.lastname: Bruno
authors.affiliation: Department of Biochemistry, Weill Cornell Medical College, New York, NY 10065.
authors.forename: Alexandria
authors.identifier: 0000-0002-6477-1758
authors.initials: A
authors.lastname: Brumfield
authors.affiliation: Department of Biochemistry, Weill Cornell Medical College, New York, NY 10065.
authors.forename: Natasha
authors.initials: N
authors.lastname: Chaudhary
authors.affiliation: Department of Biochemistry, Weill Cornell Medical College, New York, NY 10065.
authors.forename: David
authors.initials: D
authors.lastname: Iaea
authors.affiliation: Department of Biochemistry, Weill Cornell Medical College, New York, NY 10065 Department of Cardiothoracic Surgery, Weill Cornell Medical College, New York, NY 10065 temcgraw@med.cornell.edu.
authors.forename: Timothy E
authors.initials: TE
authors.lastname: McGraw
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D011992:Endosomes / Q000187:drug effects / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000378:metabolism; D055785:Gene Knockdown Techniques; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D006056:Golgi Apparatus / Q000187:drug effects / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D013058:Mass Spectrometry; D051379:Mice; D008954:Models, Biological; D011485:Protein Binding / Q000187:drug effects; D025941:Protein Interaction Mapping; D021381:Protein Transport / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D033921:Vesicular Transport Proteins / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D020690:GTPase-Activating Proteins; D051275:Glucose Transporter Type 4; D007328:Insulin; C000619639:Sec16a protein, mouse; C505647:Tbc1d4 protein, mouse; D033921:Vesicular Transport Proteins; D049452:Green Fluorescent Proteins; C520736:Rab10 protein, mouse; D020691:rab GTP-Binding Proteins