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

• 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
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 開口分泌 / リン酸化 / インスリン / Akt / GLUT4 / SNARE

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.

Research Products

• [Journal Article] Efficient regulation of branching morphogenesis via fibroblast growth factor receptor 2c in early-stage embryonic mouse salivary glands. (2016)
  • Author(s): Shibuya M., Ikari T., Sugiyama G., Ohyama Y., Kumamaru W., Nagano K., Sugiura T., Shirasuna K. and Mori Y.
  • Journal Title: Differentiation Volume: 92(4) Issue: 4 Pages: 216-224
  • DOI: 10.1016/j.diff.2016.05.005
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Tomosyn is a novel Akt substrate mediating insulin-dependent GLUT4 exocytosis. (2015)
  • Author(s): Nagano, K., Takeuchi, H., Gao, J., Mori, Y., Otani, T., Wang, D. and Hirata, M.
  • Journal Title: The International Journal of Biochemistry & Cell Biology Volume: 62 Pages: 62-71
  • DOI: 10.1016/j.biocel.2015.02.013
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Promotion of insulin-induced glucose uptake in C2C12 myotubes by osteocalcin. (2015)
  • Author(s): Tsuka, S., Aonuma, F., Higashi, S., Ohsumi, T., Nagano, K., Mizokami, A., Kawakubo-Yasukochi, T., Masaki, C., Hosokawa, R. and Hirata, M. and Takeuchi, H.
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 459 Issue: 3 Pages: 437-442
  • DOI: 10.1016/j.bbrc.2015.02.123
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Crosstalk between Bmpr1a-mediated signaling and mechanical signaling in osteocytes. (2017)
  • Author(s): Nagano K., Kohn. D. and Mishina Y.
  • Organizer: Research Day 2017
  • Place of Presentation: Michigan, USA
  • Int'l Joint Research