Role of insulin-dependent cortical fodrin/spectrin remodeling in glucose transporter 4 translocation in rat adipocytes.
Fodrin or nonerythroid spectrin is an abundant component of the cortical cytoskeletal network in rat adipocytes. Fodrin has a highly punctate distribution in resting cells, and insulin causes a dramatic remodeling of fodrin to a more diffuse pattern. Insulin-mediated remodeling of actin occurs to a lesser extent than does that of fodrin. We show that fodrin interacts with the t-soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) syntaxin 4, and this interaction is increased by insulin stimulation and decreased by prior latrunculin A treatment. Latrunculin A disrupts all actin filaments, inhibits glucose transporter 4 (GLUT4) translocation, and causes fodrin to partially redistribute from the plasma membrane to the cytosol. In contrast, cytochalasin D disrupts only the short actin filament signal, and cytochalasin D neither inhibits GLUT4 translocation nor fodrin redistribution in adipocytes. Together, our data suggest that insulin induces remodeling of the fodrin-actin network, which is required for the fusion of GLUT4 storage vesicles with the plasma membrane by permitting their access to the t-SNARE syntaxin 4.
Liu
Libin
L
Department of Biochemistry, Boston University Medical School, Boston, MA 02118, USA.
Jedrychowski
Mark P
MP
Gygi
Steven P
SP
Pilch
Paul F
PF
D000199:Actins / Q000378:metabolism; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism*; D015638:Cytochalasin D / Q000494:pharmacology; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D008840:Microfilament Proteins / Q000378:metabolism*; D008954:Models, Biological; D021381:Protein Transport; D050765:Qa-SNARE Proteins / Q000378:metabolism; D051381:Rats; D013049:Spectrin / Q000502:physiology*; D053778:Thiazolidines / Q000494:pharmacology
D000199:Actins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002352:Carrier Proteins; D015638:Cytochalasin D; D051275:Glucose Transporter Type 4; D007328:Insulin; D008840:Microfilament Proteins; D050765:Qa-SNARE Proteins; D013049:Spectrin; D053778:Thiazolidines; C037067:latrunculin A