C2 Domain-Containing Phosphoprotein CDP138 Regulates GLUT4 Insertion into the Plasma Membrane

    Authors

    X. Y. Xie; Z. W. Gong; V. Mansuy-Aubert; Q. L. Zhou; S. A. Tatulian; D. Sehrt; F. Gnad; L. M. Brill; K. Motamedchaboki; Y. Chen; M. P. Czech; M. Mann; M. Kruger;Z. Y. Jiang

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    Abbreviated Journal Title

    Cell Metab.

    Keywords

    PROTEIN-KINASE B; INSULIN SIGNALING PATHWAY; GTPASE-ACTIVATING-PROTEIN; GLUT4-CONTAINING VESICLES; GLUCOSE-TRANSPORTER; 3T3-L1 ADIPOCYTES; TRANSLOCATION; PHOSPHORYLATION; FUSION; AKT2; Cell Biology; Endocrinology & Metabolism

    Abstract

    The protein kinase B-beta (Akt2) pathway is known to mediate insulin-stimulated glucose transport through increasing glucose transporter GLUT4 translocation from intracellular stores to the plasma membrane (PM). Combining quantitative phosphoproteomics with RNAi-based functional analyses, we show that a previously uncharacterized 138 kDa C2 domain-containing phosphoprotein (CDP138) is a substrate for Akt2, and is required for optimal insulin-stimulated glucose transport, GLUT4 translocation, and fusion of GLUT4 vesicles with the PM in live adipocytes. The purified C2 domain is capable of binding Ca2+ and lipid membranes. CDP138 mutants lacking the Ca2+-binding sites. in the C2 domain or Akt2 phosphorylation site S197 inhibit insulin-stimulated GLUT4 insertion into the PM, a rate-limiting step of GLUT4 translocation. Interestingly, CDP138 is dynamically associated with the PM and GLUT4-containing vesicles in response to insulin stimulation. Together, these results suggest that CDP138 is a key molecule linking the Akt2 pathway to the regulation of GLUT4 vesicle-PM fusion.

    Journal Title

    Cell Metabolism

    Volume

    14

    Issue/Number

    3

    Publication Date

    1-1-2011

    Document Type

    Article

    Language

    English

    First Page

    378

    Last Page

    389

    WOS Identifier

    WOS:000295660200012

    ISSN

    1550-4131

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