The role of a novel Akt substrate mediating insulin-dependent exocytosis

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K20374
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Functional basic dentistry
• Research Institution: Kyushu University
• Principal Investigator: Nagano Koki 九州大学, 歯学研究院, 特別研究員 (60737089)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: 開口分泌 / リン酸化 / インスリン / Akt

Outline of Final Research Achievements

In the present study, we investigated the molecular mechanisms by which insulin signaling regulate exocytosis-related protein tomosyn, which is implicated in type 2 diabetes. We found that tomosyn on Ser-783 (S783) was phosphorylated by protein kinase Akt, which is activated by insulin signaling. The amount of tomosyn bound to SNARE [soluble NSF (N-ethylmaleimide-sensitive factor)-attachment protein receptors] protein syntaxin4, which is related to GLUT4 (glucose transporter 4) vesicle translocation, was reduced by phosphorylation at Ser-783 by Akt. Insulin stimulation increased GLUT4 in the cell surface to promote glucose uptake, however exogenous expression of the mutant tomosyn attenuated the increase by insulin. Collectively, these results suggest that Ser-783 of tomosyn is a target of Akt and is implicated in the interaction with syntaxin 4, resulting in the modulation of GLUT4 translocation.

Free Research Field

医歯薬学