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

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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

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Phosphoproteins
Cell Membrane
Insulin
Glucose
Proto-Oncogene Proteins c-akt
Membrane Fusion
Facilitative Glucose Transport Proteins
Membrane Lipids
RNA Interference
Adipocytes
Binding Sites
Phosphorylation
C2 Domains

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology

Cite this

C2 domain-containing phosphoprotein CDP138 regulates GLUT4 insertion into the plasma membrane. / Xie, Xiangyang; Gong, Zhenwei; Mansuy-Aubert, Virginie; Zhou, Qiong L.; Tatulian, Suren A.; Sehrt, Daniel; Gnad, Florian; Brill, Laurence M.; Motamedchaboki, Khatereh; Chen, Yu; Czech, Michael P.; Mann, Matthias; Krüger, Marcus; Jiang, Zhen Y.

In: Cell Metabolism, Vol. 14, No. 3, 07.09.2011, p. 378-389.

Research output: Contribution to journalArticle

Xie, X, Gong, Z, Mansuy-Aubert, V, Zhou, QL, Tatulian, SA, Sehrt, D, Gnad, F, Brill, LM, Motamedchaboki, K, Chen, Y, Czech, MP, Mann, M, Krüger, M & Jiang, ZY 2011, 'C2 domain-containing phosphoprotein CDP138 regulates GLUT4 insertion into the plasma membrane', Cell Metabolism, vol. 14, no. 3, pp. 378-389. https://doi.org/10.1016/j.cmet.2011.06.015
Xie, Xiangyang ; Gong, Zhenwei ; Mansuy-Aubert, Virginie ; Zhou, Qiong L. ; Tatulian, Suren A. ; Sehrt, Daniel ; Gnad, Florian ; Brill, Laurence M. ; Motamedchaboki, Khatereh ; Chen, Yu ; Czech, Michael P. ; Mann, Matthias ; Krüger, Marcus ; Jiang, Zhen Y. / C2 domain-containing phosphoprotein CDP138 regulates GLUT4 insertion into the plasma membrane. In: Cell Metabolism. 2011 ; Vol. 14, No. 3. pp. 378-389.
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