title: Caveolin-1 induces formation of membrane tubules that sense actomyosin tension and are inhibited by polymerase I and transcript release factor/cavin-1.
abstract: Caveolin-1 and caveolae are often lost in cancer. We found that levels of caveolin-1 and polymerase I and transcript release factor (PTRF)/cavin-1 correlated closely in a panel of cancer and normal cells. Caveolin-1 reexpression in cancer cells lacking both proteins induced formation of long membrane tubules rarely seen in normal cells. PTRF/cavin-1 inhibited tubule formation when coexpressed with caveolin-1 in these cells, whereas suppression of PTRF/cavin-1 expression in cells that normally expressed both genes stimulated tubule formation by endogenous caveolin-1. Caveolin-1 tubules shared several features with previously described Rab8 tubules. Coexpressed Rab8 and caveolin-1 labeled the same tubules (as did EHD proteins), and synergized to promote tubule formation, whereas a dominant-interfering Rab8 mutant inhibited caveolin-1 tubule formation. Both overexpression and inhibition of dynamin-2 reduced the abundance of caveolin-1 tubules. Caveolin-1 reexpression in SK-BR-3 breast cancer cells also induced formation of short membrane tubules close to cortical actin filaments, which required actin filaments but not microtubules. Actomyosin-induced tension destabilized both long and short tubules; they often snapped and resolved to small vesicles. Actin filament depolymerization or myosin II inhibition reduced tension and stabilized tubules. These data demonstrate a new function for PTRF/cavin-1, a new functional interaction between caveolin-1 and Rab8 and that actomyosin interactions can induce tension on caveolin-1-containing membranes.
authors.affiliation: Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794-5215, USA.
authors.forename: Prakhar
authors.initials: P
authors.lastname: Verma
authors.forename: Anne G
authors.initials: AG
authors.lastname: Ostermeyer-Fay
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Brown
mesh_terms: D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000235:genetics / Q000378:metabolism; D000205:Actomyosin / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure*; D002784:Cholesterol / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D004256:DNA Polymerase I / Q000378:metabolism*; D034285:Dynamin II / Q000235:genetics / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology; D006801:Humans; D008870:Microtubules / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013314:Stress, Mechanical; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000089982:ADP-Ribosylation Factor 6; C497835:CAVIN1 protein, human; D051242:Caveolin 1; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D000205:Actomyosin; D002784:Cholesterol; D004256:DNA Polymerase I; C082377:RAB8A protein, human; D020727:ADP-Ribosylation Factors; D020691:rab GTP-Binding Proteins; D034285:Dynamin II