Synip phosphorylation is required for insulin-stimulated Glut4 translocation and glucose uptake in podocyte.
Previously we reported that the phosphorylation of Synip on serine 99 is required for Synip dissociation from Syntaxin4 and insulin-stimulated Glut4 translocation in cultured 3T3-L1 adipocytes. We also reported that the dissociated Synip remains anchored to the plasma membrane by binding to Phosphatidylinositol (3,4,5)-triphosphate. Recently Synip was reported to arrest SNARE-dependent membrane fusion as a selective t-SNARE binding inhibitor. In this study, we have found that Synip is expressed in podocytes although at a somewhat lower level than in adipocytes. To determine whether phosphorylation of Synip on serine 99 is required for insulin-stimulated Glut4 translocation and glucose uptake in podocytes we expressed a phosphorylation deficient Synip mutant (S99A-Synip) that inhibited insulin-stimulated Glut4 translocation and 2-deoxyglucose uptake in adipocytes. We conclude that serine 99 phosphorylation of Synip is required for Glut4 translocation and glucose uptake in both adipocytes and podocytes, suggesting that defects in Synip phosphorylation may underlie insulin resistance and associated diabetic nephropathy.
Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan.
Eijiro
E
Yamada
Tsugumichi
T
Saito
Shuichi
S
Okada
Hiroki
H
Takahashi
Kihachi
K
Ohshima
Koshi
K
Hashimoto
Tetsurou
T
Satoh
Masatomo
M
Mori
Junichi
J
Okada
Masanobu
M
Yamada
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D051379:Mice; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010766:Phosphorylation; D050199:Podocytes / Q000187:drug effects* / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D021381:Protein Transport / Q000187:drug effects; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*
D051275:Glucose Transporter Type 4; D007328:Insulin; C495693:Slc2a4 protein, mouse; C120000:Stxbp4 protein, mouse; D033921:Vesicular Transport Proteins; D051058:Oncogene Protein v-akt; D005947:Glucose