Elucidation of macropinocytosis-mediated repulsive axon guidance and its application to the treatment of spinal cord injury

• Project/Area Number: 23590274
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General physiology
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: KABAYAMA Hiroyuki 独立行政法人理化学研究所, 脳科学総合研究センター, 研究員 (10332339)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: マクロピノサイトーシス / エンドサイトーシス / 反発性軸索誘導 / 成長円錐 / 膜動態 / Sema3a / syntaxin-1B / syntaxin / syntaxin1B / neurotoxin C1

Research Abstract

Growth cone collapse is a crucial process for repulsive axon guidance and is accompanied by a reduction in growth cone surface area. This process of reduction may be regulated by endocytosis; however, its molecular mechanism is unclear. Macropinocytosis is a clathrin-independent form of endocytosis in which large areas of plasma membrane can be engulfed. We examined the effects of macropinocytosis inhibitor, ethylisopropylamiloride (EIPA) on Sema3A-induced growth cone collapse in chicken dorsal root ganglion neurons. We found that EIPA suppressed Sema3A-induced macropinocytosis (uptake of high-molecular weight dextran) and growth cone collapse, as shown in Figure 1. These results indicate that macropinocytosis-mediated massive internalization of the plasma membrane is required for Sema3A-induced growth cone collapse.

Research Products

• [Journal Article] Syntaxin 1B Suppresses Macropinocytosis and Semaphorin 3A-Induced Growth Cone Collapse (2011)
  • Author(s): Kabayama H
  • Journal Title: J Neurosci Volume: 31(20) Issue: 20 Pages: 7357-64
  • DOI: 10.1523/jneurosci.2718-10.2011
  • Peer Reviewed
• [Journal Article] Inositol 1,4,5-trisphosphate receptor interacts with the SNARE domain of syntaxin 1B (2011)
  • Author(s): Tanaka S
  • Journal Title: J Physiol Sci Volume: 61(3) Issue: 3 Pages: 221-9
  • DOI: 10.1007/s12576-011-0140-4
  • Peer Reviewed
• [Journal Article] Dissociation of inositol polyphosphates from the C2B domain of synaptotagmin facilitates spontaneous release of catechol amines in adrenal chromaffin cells. A suggestive evidence of a fusion clamp by synaptotagmin (2011)
  • Author(s): Sasakawa N
  • Journal Title: Neuropharmacology Volume: 60(7-8) Issue: 7-8 Pages: 1364-70
  • DOI: 10.1016/j.neuropharm.2011.03.005
  • Peer Reviewed
• [Presentation] Macropinocytosis mediates Sema3A-induced growth cone collapse (2013)
  • Author(s): Kabayama Hiroyuki, Takeuchi Makoto, Taniguchi Masahiko, Tokushige Naoko, Kozaki Shunji, Mizutani Akihiro, Nakamura Takeshi, Mikoshiba Katsuhiko
  • Organizer: 18th International Conference on Calcium Binding Proteins and Calcium Function in Health and Disease
  • Place of Presentation: Kiruna, Sweden
  • Year and Date: 2013-06-30
• [Presentation] シンタキシン1B調節性マクロピノサイトーシスを介したセマフォリン3Aによる成長円錐の退縮 (2011)
  • Author(s): 樺山博之, 竹内誠, 谷口雅彦, 徳重直子, 小崎俊司, 水谷顕洋, 中村健, 御子柴克彦
  • Organizer: 第34回日本神経科学大会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2011-09-17
• [Presentation] シンタキシン1B調節性マクロピノサイトーシスを介したセマフォリン3Aによる成長円錐の退縮
  • Author(s): 樺山 博之、 竹内 誠 、 谷口 雅彦、 徳重 直子、 小崎 俊司、 水谷 顕洋、 中村 健 、 御子柴 克彦
  • Organizer: 第３４回日本神経科学大会
  • Place of Presentation: パシフィコ横浜
• [Remarks] 所属研究室ホームページ
  • URL: http://mikoshiba-lab.brain.riken.jp/indexj.html
• [Remarks] Frontiers誌ホームページ
  • URL: http://community.frontiersin.org/people/HiroyukiKabayama/98808
• [Remarks] Frontiers in Membrane Physiology and Membrane Biophysics誌にて, マクロピノサイトーシス関連研究をテーマにしたResearch Topic, Physiological roles and regulatory mechanisms of macropinocytosis-mediated membrane retrieval in health and disease,をguest associate editorとしてオーガナイズ
  • URL: http://www.frontiersin.org/Journal/SpecialTopicDetail.aspx?name=membrane_physiology_and_membrane_biophysics&st=2047&sname=Physiological_roles_and_regula
• [Remarks] 研究紹介記事
  • URL: http://www.riken.jp/en/research/rikenresearch/highlights/6677
• [Remarks] 研究プレス発表理化学研究所
  • URL: http://www.riken.jp/pr/press/2011/20110518/
• [Remarks] 科学技術振興機構
  • URL: http://www.jst.go.jp/pr/announce/20110518/index.html?utm_medium=twitter
• [Remarks] 研究紹介テレビ番組2011, June 25魔法の金属,'カルシウム',サイエンスゼロ, NHK.御子柴克彦, 樺山博之(研究成果であるマクロピノサイトーシス依存的な神経回路形成の解説)2013. May 15 NHK WORLD Katsuhiko Mikoshiba, Hiroyuki Kabayama
  • URL: http://www3.nhk.or.jp/nhkworld/english/tv/scienceview/archives20130515.html
• [Remarks] 理化学研究所発生神経生物研究チーム
  • URL: http://www.brain.riken.jp/jp/faculty/details/29
• [Remarks] 科学技術振興機構
  • URL: http://www.jst.go.jp/pr/announce/20110518/index.html
• [Patent(Industrial Property Rights)] METHOD OF REGULATING NEURONAL AXON ELONGATION (2013)
  • Inventor(s): Katsuhiko Mikoshiba, Hiroyuki Kabayama
  • Industrial Property Rights Holder: RIKEN
  • Industrial Property Rights Type: 特許
  • Filing Date: 2013
  • Overseas
• [Patent(Industrial Property Rights)] METHOD OF REGULATING NERVE-CELL GROWTH (2013)
  • Inventor(s): K. Mikoshiba, H. Kabayama
  • Industrial Property Rights Holder: 理化学研究所
  • Industrial Property Rights Type: 特許
  • Filing Date: 2013-04-15
  • Overseas