IGF-I induced rapid recruitment of integrin beta1 to lipid rafts is Caveolin-1 dependent.
Caveolin-1 (Cav-1) regulates both insulin like growth factor receptor (IGF-IR) and integrin beta1 function. However, the role of Cav-1 in IGF-IR/integrin beta1 cross talk remains to be established. In this study, we observed that IGF-I did not induce integrin beta1 internalization but its plasma membrane reorganization. In particular, we found a rapid and transient association between integrin beta1 and Cav-1 followed by the enrichment of integrin beta1 in lipid rafts. To determine the role of Cav-1 in this process, we transfected Hacat cells with small interfering RNA specific for Cav-1 (siRNA-Cav-1) and with a scrambled siRNA as control (siRNA-Ctr). Cav-1 down regulated Hacat cells were then stimulated with IGF-I and analyzed by immunofluorescence and flow cytometry. We found that Cav-1 silencing abolished the recruitment of integrin beta1 to lipid rafts in the presence of IGF-I. These data demonstrate that IGF-IR/integrin beta1 cross talk is followed by integrin beta1 lipid raft compartmentalization and that Cav-1 is required for this process.
Salani
B
B
Department of Endocrinology and Medicine (DiSEM), University of Genova, Viale Benedetto XV, 6, 16132 Genova, Italy.
Briatore
L
L
Contini
P
P
Passalacqua
M
M
Melloni
E
E
Paggi
A
A
Cordera
R
R
Maggi
D
D
D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D047468:Immunoprecipitation; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D019012:Integrin beta1 / Q000378:metabolism*; D021962:Membrane Microdomains / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D014162:Transfection
C495540:CAV1 protein, human; D051242:Caveolin 1; D019012:Integrin beta1; D034741:RNA, Small Interfering; D007334:Insulin-Like Growth Factor I