Syntaxin4 interacting protein (Synip) binds phosphatidylinositol (3,4,5) triphosphate

Tsugumichi Saito, Shuichi Okada, Atsushi Nohara, Yuko Tagaya, Aya Osaki, Shinsuke Oh-i, Hiroki Takahashi, Takafumi Tsuchiya, Koshi Hashimoto, Tetsurou Satoh, Masanobu Yamada, Jeffrey E. Pessin, Masatomo Mori

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

The insulin responsive Glut4 transport vesicles contain the v-SNARE protein Vamp2 that associate with the plasma membrane t-SNARE protein Syntaxin 4 to drive insulin-stimulated Glut4 translocation in skeletal muscle and adipocytes. The syntaxin 4 interacting protein (Synip) binds to syntaxin 4 in the basal state and dissociates in the insulin-stimulated state allowing for the subsequent binding of Vamp2 containing Glut4 vesicles and fusion with the plasma membrane. In this study, we have found that Synip binds phosphatidylinositol 3,4,5-triphosphate (PIP3), but not phosphatidylinositol 3 phosphate (PIP) or phosphatidylinositol 3,4-biphosphate (PIP2) through the Synip WW domain as deletion of this domain (Synip ΔWW) failed to bind PIP3. Over-expressed Synip ΔWW in 3T3L1 adipocytes reduced the basal levels of Glut4 at the plasma membrane with no effect on the binding to syntaxin 4 in vitro. Subcellular fractionation demonstrated that the amount of Synip ΔWW at the PM was decreased in response to insulin in 3T3L1 adipocytes whereas the amount of Synip WT increased. These data suggest that in the presence of insulin, the dissociated Synip remains anchored to the plasma membrane by binding to PIP3.

Original languageEnglish (US)
Article numbere42782
JournalPloS one
Volume7
Issue number8
DOIs
StatePublished - Aug 3 2012

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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    Saito, T., Okada, S., Nohara, A., Tagaya, Y., Osaki, A., Oh-i, S., Takahashi, H., Tsuchiya, T., Hashimoto, K., Satoh, T., Yamada, M., Pessin, J. E., & Mori, M. (2012). Syntaxin4 interacting protein (Synip) binds phosphatidylinositol (3,4,5) triphosphate. PloS one, 7(8), [e42782]. https://doi.org/10.1371/journal.pone.0042782