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

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Authors: 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.; Kruger, M.; Jiang, Z. Y.
Article Title: C2 domain-containing phosphoprotein CDP138 regulates GLUT4 insertion into the plasma membrane
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 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.
Journal Title: Cell metabolism
Volume: 14
Issue: 3
ISSN: 1932-7420; 1550-4131
Publisher: Elsevier Inc  
Journal Place: United States
Date Published: 2011
Start Page: 378
End Page: 389
Language: eng
DOI/URL:

10.1016/j.cmet.2011.06.015
Notes: LR: 20141022; CI: Copyright (c) 2011; GR: DK060564/DK/NIDDK NIH HHS/United States; GR: P01 DK060564/DK/NIDDK NIH HHS/United States; GR: P01 DK060564-01/DK/NIDDK NIH HHS/United States; JID: 101233170; 0 (Glucose Transporter Type 4); 0 (Insulin); 0 (Peptides); 0 (Phosphoproteins); 0 (RNA, Small Interfering); 0 (Slc2a4 protein, mouse); EC 2.7.11.1 (Akt2 protein, mouse); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); SY7Q814VUP (Calcium); NIHMS318687; OID: NLM: NIHMS318687; OID: NLM: PMC3172579; 2010/12/08 [received]; 2011/05/03 [revised]; 2011/06/09 [accepted]; ppublish