Localization of the insulin receptor in caveolae of adipocyte plasma membrane

  • Johanna Gustavsson
    Department of Cell Biology Linköping University S‐58185 Linköping Sweden
  • Santiago Parpal
    Department of Cell Biology Linköping University S‐58185 Linköping Sweden
  • Margareta Karlsson
    Department of Cell Biology Linköping University S‐58185 Linköping Sweden
  • Cecilia Ramsing
    Department of Cell Biology Linköping University S‐58185 Linköping Sweden
  • Hans Thorn
    Department of Cell Biology Linköping University S‐58185 Linköping Sweden
  • Marie Borg
    Department of Cell Biology Linköping University S‐58185 Linköping Sweden
  • Margaretha Lindroth
    Department of Cell Biology Linköping University S‐58185 Linköping Sweden
  • Kajsa Holmgren Peterson
    Department of Medical Microbiology Faculty of Health Sciences Linköping University S‐58185 Linköping Sweden
  • Karl‐Eric Magnusson
    Department of Medical Microbiology Faculty of Health Sciences Linköping University S‐58185 Linköping Sweden
  • Peter Strålfors
    Department of Cell Biology Linköping University S‐58185 Linköping Sweden

書誌事項

公開日
1999-11
権利情報
  • http://onlinelibrary.wiley.com/termsAndConditions#vor
DOI
  • 10.1096/fasebj.13.14.1961
公開者
Wiley

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説明

<jats:title>ABSTRACT</jats:title> <jats:p> The insulin receptor is a transmembrane protein of the plasma membrane, where it recognizes extracellular insulin and transmits signals into the cellular signaling network. We report that insulin receptors are localized and signal in caveolae microdomains of adipocyte plasma membrane. Immunogold electron microscopy and immunofluorescence microscopy show that insulin receptors are restricted to caveolae and are colocalized with caveolin over the plasma membrane. Insulin receptor was enriched in a caveolae‐enriched fraction of plasma membrane. By extraction with β‐cyclodextrin or destruction with cholesterol oxidase, cholesterol reduction attenuated insulin receptor signaling to protein phosphorylation or glucose transport. Insulin signaling was regained by spontaneous recovery or by exogenous replenishment of cholesterol. β‐Cyclodextrin treatment caused a nearly complete annihilation of caveolae invaginations as examined by electron microscopy. This suggests that the receptor is dependent on the caveolae environment for signaling. Insulin stimulation of cells prior to isolation of caveolae or insulin stimulation of the isolated caveolae fraction increased tyrosine phosphorylation of the insulin receptor in caveolae, demonstrating that insulin receptors in caveolae are functional. Our results indicate that insulin receptors are localized to caveolae in the plasma membrane of adipocytes, are signaling in caveolae, and are dependent on caveolae for signaling.—Gustavsson, J., Parpal, S., Karlsson, M., Ramsing, C., Thorn, H., Borg, M., Lindroth, M., Peterson, K. H., Magnusson, K.‐E., Strålfors, P. Localization of the insulin receptor in caveolae of adipocyte plasma membrane. <jats:italic>FASEB J</jats:italic> . 13, 1961–1971 (1999) </jats:p>

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