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

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 th...

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Main Authors: 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
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3411842?pdf=render
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author 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
author_facet 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
author_sort Tsugumichi Saito
collection DOAJ
description 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.
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spelling doaj.art-6bc5077bb32c41da8a51c9df733df4962022-12-22T00:45:03ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0178e4278210.1371/journal.pone.0042782Syntaxin4 interacting protein (Synip) binds phosphatidylinositol (3,4,5) triphosphate.Tsugumichi SaitoShuichi OkadaAtsushi NoharaYuko TagayaAya OsakiShinsuke Oh-IHiroki TakahashiTakafumi TsuchiyaKoshi HashimotoTetsurou SatohMasanobu YamadaJeffrey E PessinMasatomo MoriThe 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.http://europepmc.org/articles/PMC3411842?pdf=render
spellingShingle 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
Syntaxin4 interacting protein (Synip) binds phosphatidylinositol (3,4,5) triphosphate.
PLoS ONE
title Syntaxin4 interacting protein (Synip) binds phosphatidylinositol (3,4,5) triphosphate.
title_full Syntaxin4 interacting protein (Synip) binds phosphatidylinositol (3,4,5) triphosphate.
title_fullStr Syntaxin4 interacting protein (Synip) binds phosphatidylinositol (3,4,5) triphosphate.
title_full_unstemmed Syntaxin4 interacting protein (Synip) binds phosphatidylinositol (3,4,5) triphosphate.
title_short Syntaxin4 interacting protein (Synip) binds phosphatidylinositol (3,4,5) triphosphate.
title_sort syntaxin4 interacting protein synip binds phosphatidylinositol 3 4 5 triphosphate
url http://europepmc.org/articles/PMC3411842?pdf=render
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