C2 domain-containing phosphoprotein CDP138 regulates GLUT4 insertion into the plasma membrane

Xiangyang Xie, Zhenwei Gong, Virginie Mansuy-Aubert, Qiong L. Zhou, Suren A. Tatulian, Daniel Sehrt, Florian Gnad, Laurence M. Brill, Khatereh Motamedchaboki, Yu Chen, Michael P. Czech, Matthias Mann, Marcus Krüger, Zhen Y. Jiang

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

The protein kinase B β (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 Ca 2+ and lipid membranes. CDP138 mutants lacking the Ca 2+-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.

Original languageEnglish (US)
Pages (from-to)378-389
Number of pages12
JournalCell Metabolism
Volume14
Issue number3
DOIs
StatePublished - Sep 7 2011

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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    Xie, X., Gong, Z., Mansuy-Aubert, V., Zhou, Q. L., Tatulian, S. A., Sehrt, D., Gnad, F., Brill, L. M., Motamedchaboki, K., Chen, Y., Czech, M. P., Mann, M., Krüger, M., & Jiang, Z. Y. (2011). C2 domain-containing phosphoprotein CDP138 regulates GLUT4 insertion into the plasma membrane. Cell Metabolism, 14(3), 378-389. https://doi.org/10.1016/j.cmet.2011.06.015