Elucidation of macropinocytosis-mediated neural circuit formation

• Project/Area Number: 26460309
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General physiology
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Kabayama Hiroyuki 国立研究開発法人理化学研究所, 脳科学総合研究センター, 研究員 (10332339)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: マクロピノサイトーシス / 膜動態 / syntaxin1B / IP3R / 反発性軸索誘導 / 神経回路形成 / syntaxin / エンドサイトーシス / 成長円錐 / 成長円錐退縮

Outline of Final Research Achievements

During development, a repulsive axon guidance cue semaphorin 3A (sema3A)-induced growth cone collapse is caused by macropinocytosis-mediated membrane retrieval. I have identified syntaxin1B as negative regulator of macropinocytosis in growth cones. In this study, I focused on the molecular mechanism of syntaxin1B-mediated macropinocytosis and found that syntaxin1B regulates the function of IP3R1 by binding with coiled-coil domain of IP3R1, thereby mediating Ca2+-dependent macropinocytosis.

Research Products

• [Journal Article] Parkin promotes proteasomal degradation of synaptotagmin IV by accelerating polyubiquitination. (2017)
  • Author(s): Kabayama, H., Tokushige, N., Takeuchi, M., Kabayama, M., Fukuda M. and Mikoshiba, K.
  • Journal Title: Mol. Cell. Neurosci. Volume: 80 Pages: 89-99
  • DOI: 10.1016/j.mcn.2017.02.006
  • Peer Reviewed
• [Presentation] Macropinocytosis mediates Sema3A-induced growth cone collapse (2014)
  • Author(s): Kabayama Hiroyuki, Takeuchi Makoto, Taniguchi Masahiko, Tokushige Naoko, Kozaki Shunji, Mizutani Akihiro, Hirohide Iwasaki, Nakamura Takeshi, and Mikoshiba Katsuhiko
  • Organizer: Calcium Signaling: from basic to bedside 2014
  • Place of Presentation: Stockholm, Sweden
  • Year and Date: 2014-07-03 – 2014-07-05