title: A novel actin cytoskeleton-dependent noncaveolar microdomain composed of homo-oligomeric caveolin-2 for activation of insulin signaling.
abstract: The role of caveolin-2 (cav-2), independently of caveolin-1 (cav-1) and caveolae, has remained elusive. Our data show that cav-2 exists in the plasma membrane (PM) in cells lacking cav-1 and forms homo-oligomeric complexes. Cav-2 did not interact with cavin-1 and cavin-2 in the PM. Rab6-GTP was required for the microtubule-dependent exocytic transport of cav-2 from the Golgi to the PM independently of cav-1. The cav-2-oligomerized noncaveolar microdomain was unaffected by cholesterol depletion and protected from shearing of silica-coated PM. Activation of insulin receptor (IR) was processed in the microdomain. Actin depolymerization affected the formation and sustenance of cav-2-oligomerized noncaveolar microdomain and attenuated IR recruitment to the microdomain thereby inhibiting IR signaling activation. Cav-2 shRNA stable cells and the cells ectopically expressing an oligomerization domain truncation mutant, cav-2∆47-86 exhibited retardation of IR signaling activation via the noncaveolar microdomain. Elevation in status of cav-2 expression rendered the noncaveolar activation of IR signaling in cav-1 down-regulated or/and cholesterol-depleted cells. Our findings reveal a novel homo-oligomeric cav-2 microdomain responsible for regulating activation of IR signaling in the PM.
authors.affiliation: Department of Biochemistry, Gyeongsang National University, Jinju, Republic of Korea.
authors.forename: Hayeong
authors.initials: H
authors.lastname: Kwon
authors.forename: Jaewoong
authors.initials: J
authors.lastname: Lee
authors.forename: Kyuho
authors.initials: K
authors.lastname: Jeong
authors.forename: Donghwan
authors.initials: D
authors.lastname: Jang
authors.forename: Yunbae
authors.initials: Y
authors.lastname: Pak
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D015153:Blotting, Western; D021941:Caveolae / Q000378:metabolism; D051242:Caveolin 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051243:Caveolin 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism; D047468:Immunoprecipitation; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D021962:Membrane Microdomains / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D011972:Receptor, Insulin / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013347:Subcellular Fractions
chemical_list: D051242:Caveolin 1; D051243:Caveolin 2; D007328:Insulin; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D006160:Guanosine Triphosphate; D011972:Receptor, Insulin
keywords: Actin cytoskeleton; CCD; CTB; Cav-1; Cav-2; Caveolin-2; GPMV; HLDM; IR; Insulin receptor; LDMV; LLDM; LatB; Microtubules; MβCD; Noncaveolar microdomain; PM; Rab6; TfR; caveolin-1; caveolin-2; cholera toxin B subunit; cytochalasin D; giant plasma membrane vesicle; heavy low-density insoluble membrane; insulin receptor; latrunculin B; light low-density insoluble membrane; low density membrane vesicle; methyl-β-cyclodextrin; plasma membrane; transferrin receptor