Dissociation of the insulin receptor and caveolin-1 complex by ganglioside GM3 in the state of insulin resistance

DOI HANDLE Web Site PubMed 被引用文献65件 オープンアクセス
  • Kazuya Kabayama
    *Division of Glycopathology, Institute of Molecular Biomembranes and Glycobiology, Tohoku Pharmaceutical University, 4-4-1, Komatsushima, Aoba-ku, Sendai 981-8558, Miyagi, Japan;
  • Takashige Sato
    Department of Biomembrane and Biofunctional Chemistry, School of Pharmaceutical Sciences and Pharmacy, and
  • Kumiko Saito
    Department of Biomembrane and Biofunctional Chemistry, School of Pharmaceutical Sciences and Pharmacy, and
  • Nicoletta Loberto
    Department of Medical Chemistry, Biochemistry and Biotechnology, University of Milan, Via Fratelli Cervi 93, Segrate 20090, Milan, Italy; and
  • Alessandro Prinetti
    Department of Medical Chemistry, Biochemistry and Biotechnology, University of Milan, Via Fratelli Cervi 93, Segrate 20090, Milan, Italy; and
  • Sandro Sonnino
    Department of Medical Chemistry, Biochemistry and Biotechnology, University of Milan, Via Fratelli Cervi 93, Segrate 20090, Milan, Italy; and
  • Masataka Kinjo
    Laboratory of Supramolecular Biophysics, Research Institute for Electronic Science, Hokkaido University, Nishi 6, Kita 12, Kita-ku, Sapporo 060-0812, Japan;
  • Yasuyuki Igarashi
    Department of Biomembrane and Biofunctional Chemistry, School of Pharmaceutical Sciences and Pharmacy, and
  • Jin-ichi Inokuchi
    *Division of Glycopathology, Institute of Molecular Biomembranes and Glycobiology, Tohoku Pharmaceutical University, 4-4-1, Komatsushima, Aoba-ku, Sendai 981-8558, Miyagi, Japan;

書誌事項

公開日
2007-08-21
DOI
  • 10.1073/pnas.0703650104
公開者
Proceedings of the National Academy of Sciences

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<jats:p> Membrane microdomains (lipid rafts) are now recognized as critical for proper compartmentalization of insulin signaling. We previously demonstrated that, in adipocytes in a state of TNFα-induced insulin resistance, the inhibition of insulin metabolic signaling and the elimination of insulin receptors (IR) from the caveolae microdomains were associated with an accumulation of the ganglioside GM3. To gain insight into molecular mechanisms behind interactions of IR, caveolin-1 (Cav1), and GM3 in adipocytes, we have performed immunoprecipitations, cross-linking studies of IR and GM3, and live cell studies using total internal reflection fluorescence microscopy and fluorescence recovery after photobleaching techniques. We found that ( <jats:italic>i</jats:italic> ) IR form complexes with Cav1 and GM3 independently; ( <jats:italic>ii</jats:italic> ) in GM3-enriched membranes the mobility of IR is increased by dissociation of the IR–Cav1 interaction; and ( <jats:italic>iii</jats:italic> ) the lysine residue localized just above the transmembrane domain of the IR β-subunit is essential for the interaction of IR with GM3. Because insulin metabolic signal transduction in adipocytes is known to be critically dependent on caveolae, we propose a pathological feature of insulin resistance in adipocytes caused by dissociation of the IR–Cav1 complex by the interactions of IR with GM3 in microdomains. </jats:p>

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