@article{1b05cb9f8ec441afa3334b60704216cf,
title = "C2 domain-containing phosphoprotein CDP138 regulates GLUT4 insertion into the plasma membrane",
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.",
author = "Xiangyang Xie and Zhenwei Gong and Virginie Mansuy-Aubert and Zhou, {Qiong L.} and Tatulian, {Suren A.} and Daniel Sehrt and Florian Gnad and Brill, {Laurence M.} and Khatereh Motamedchaboki and Yu Chen and Czech, {Michael P.} and Matthias Mann and Marcus Kr{\"u}ger and Jiang, {Zhen Y.}",
note = "Funding Information: We wish to thank Tao Xu for IRAP-pHluorin and GLUT4-EGFP constructs, Jennifer Lippincott-Schwartz for the fast-switching TIRFM platform, Harry Dolan (Cell Signaling Technology) for Lot-2 stock of PAS (# 9611) Ab, and Supriyo Ray for preparing lipid vesicles. We appreciate Tim Osborne, Dan Kelly, and Tod Gulick for critical reading of the manuscript and suggestions, and Shonna Hyde for administrative support. These studies were supported by SBMRI funding to Z.Y.J. Initial SILAC proteomic studies were supported by a Junior Faculty Award from the American Diabetes Association to Z.Y.J. and by NIH program project grant DK060564 to M.P.C. X.X. is supported by a James and Esther King Postdoctoral Research Fellowship. Z.Y.J. and M.K. did SILAC proteomics with M.M., F.G., and M.P.C.; Z.G., M.K., L.M.B., K.M., and Z.Y.J. did protein phosphorylation analysis. X.X. did TIRFM and confocal imaging analysis. Q.L.Z. did glucose transport assays. Z.Y.J. did widefield GLUT4 translocation assays and analyzed endogenous GLUT4 distribution with TIRFM. V.M.A. did membrane fractionation. V.M.A., S.A.T., and D.S. did Ca 2+ - and lipid-binding assays. Y.C. was involved in high-resolution imaging. Z.Y.J., M.K., X.X., Z.G., V.M.A., Q.L.Z., and S.A.T. designed experiments and analyzed data. Z.Y.J. wrote the manuscript. ",
year = "2011",
month = sep,
day = "7",
doi = "10.1016/j.cmet.2011.06.015",
language = "English (US)",
volume = "14",
pages = "378--389",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "3",
}