TAILIEUCHUNG - Báo cáo khoa học: Colocalization of insulin receptor and insulin receptor substrate-1 to caveolae in primary human adipocytes Cholesterol depletion blocks insulin signalling for metabolic and mitogenic control

Caveolae are plasma membrane invaginations with several functions, one of which appears to be to organize receptor mediated signalling. Here we report that in primary human subcutaneous adipocytes the insulin receptor was localized to caveolae by electron microscopy/immunogold detection and by isolating caveolae from plasma membranes. | Eur. J. Biochem. 271 2471-2479 2004 FEBS 2004 doi Colocalization of insulin receptor and insulin receptor substrate-1 to caveolae in primary human adipocytes Cholesterol depletion blocks insulin signalling for metabolic and mitogenic control Maraareta Karlsson1 Hans Thorn1 Anna Danielsson1 Karin G. Stenkula1 Anita Ost1. Johanna Gustavsson1 B Fredrik Hb Nystrom2 and Peter Strẵlíors1 1 Department of Cell Biology and Diabetes Research Centre and department of Medicine and Care and Diabetes Research Centre University of Linkoping Sweden Caveolae are plasma membrane invaginations with several functions one of which appears to be to organize receptor mediated signalling. Here we report that in primary human subcutaneous adipocytes the insulin receptor was localized to caveolae by electron microscopy immunogold detection and by isolating caveolae from plasma membranes. Part of insulin receptor substrate 1 IRS1 the immediate downstream signal mediator was colocalized with the insulin receptor in the plasma membrane and caveolae as demonstrated by immunofluorescence microscopy immunogold electron microscopy and immunogold electron microscopy of transfected recombinant HA-IRS1. In contrast rat epi-didymal adipocytes lacked IRS1 at the plasma membrane. Depletion of cholesterol from the cells using b-cyclodextrin blocked insulin stimulation of glucose uptake insulin inhibition of perilipin phosphorylation in response to isoproterenol and insulin stimulation of protein kinase B and Map-kinases extracellular signal-related kinase ERK 1 2 phosphorylation. Insulin-stimulated phosphorylation of the insulin receptor and IRS1 was not affected indicating that caveolae integrity is required downstream of IRS1. In conclusion we show that insulin receptor and IRS1 are both caveolar proteins and that caveolae are required for both metabolic and mitogenic control in human adipocytes. Our results establish caveolae as foci of insulin action and stress the .

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