title: Insulin triggers surface-directed trafficking of sequestered GLUT4 storage vesicles marked by Rab10.
abstract: Understanding how glucose transporter isoform 4 (GLUT4) redistributes to the plasma membrane during insulin stimulation is a major goal of glucose transporter research. GLUT4 molecules normally reside in numerous intracellular compartments, including specialized storage vesicles and early/recycling endosomes. It is unclear how these diverse compartments respond to insulin stimulation to deliver GLUT4 molecules to the plasma membrane. For example, do they fuse with each other first or remain as separate compartments with different trafficking characteristics? Our recent live cell imaging studies are helping to clarify these issues. Using Rab proteins as specific markers to distinguish between storage vesicles and endosomes containing GLUT4, we demonstrate that it is primarily internal GLUT4 storage vesicles (GSVs) marked by Rab10 that approach and fuse at the plasma membrane and GSVs don't interact with endosomes on their way to the plasma membrane. These new findings add strong support to the model that GSV release from intracellular retention plays a major role in supplying GLUT4 molecules onto the PM under insulin stimulation.
authors.affiliation: The Eugene Kennedy Shriver National Institute of Child Health and Human Development; National Institutes of Health; Bethesda, MD USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: The Eugene Kennedy Shriver National Institute of Child Health and Human Development; National Institutes of Health; Bethesda, MD USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Lippincott-Schwartz
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D011992:Endosomes / Q000187:drug effects* / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D051379:Mice; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D051275:Glucose Transporter Type 4; D007328:Insulin; D034741:RNA, Small Interfering; C538901:Rab10 protein, human; D020691:rab GTP-Binding Proteins
keywords: AS160; GLUT4; IRAP; Rab10; Rab14; TIRF; adipocytes; insulin
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