Functional Analysis of protein tyrosine phosphatase Shp2 in the adult forebrain neurons

• Project/Area Number: 25870110
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurochemistry/Neuropharmacology; General medical chemistry
• Research Institution: Tokyo Medical University (2014); Gunma University (2013)
• Principal Investigator: KUSAKARI Shinya 東京医科大学, 医学部, 助教 (10510901)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 蛋白質チロシンリン酸化 / チロシンホスファターゼ / 脳高次機能 / チロシン脱リン酸化酵素 / 高次脳機能

Outline of Final Research Achievements

The conditional-knockout (cKO) mice lacking Shp2, tyrosine phosphatase, specifically in postmitotic forebrain neurons manifest abnormal behavior, including hyperactivity. In this study, I found that novelty-induced expression of immediate-early genes and activation of extracellular-signal-regulated kinase (Erk) were attenuated in the cerebral cortex and hippocampus of Shp2 cKO mice, suggestive of reduced neuronal activity. The mutant mice also manifested transient impairment of memory formation in the Morris water maze. These results suggest that Shp2 contributes to regulation of Erk activation and synaptic plasticity in postmitotic forebrain neurons and thereby controls locomotor activity and memory formation.

Research Products

• [Journal Article] Shp2 in forebrain neurons regulates synaptic plasticity, locomotion, and memory formation in mice (2015)
  • Author(s): Kusakari S, Saitow F, Ago Y, Shibasaki K, Sato-Hashimoto, M., Matsuzaki, Y., Kotani T, Murata Y, Hirai H, Matsuda T, Suzuki H, Matozaki T, Ohnishi H
  • Journal Title: Mol. Cell. Biol. Volume: 35 Issue: 9 Pages: 1557-1572
  • DOI: 10.1128/mcb.01339-14
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Functional analysis of protein tyrosine phosphatase Shp2 in post-mitotic neurons (2014)
  • Author(s): Kusakari S 他
  • Organizer: 11th International Conference on Protein Phosphatase
  • Place of Presentation: 東北大学医学部 艮陵会館
  • Year and Date: 2014-11-12 – 2014-11-14
• [Presentation] Functional Analysis of protein tyrosine phosphatase Shp2 in the adult forebrain neurons (2014)
  • Author(s): Ohnishi H, Kusakari S 他
  • Organizer: 第３７回日本神経科学大会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-09-11 – 2014-09-13
• [Presentation] 細胞質型チロシンホスファターゼShp2による脳機能制御 (2014)
  • Author(s): 草苅伸也 他
  • Organizer: 第6回ホスファターゼ研究会学術集会
  • Place of Presentation: 三重大学
• [Presentation] 成熟脳における細胞質型チロシンホスファターゼShp2の機能解析 (2013)
  • Author(s): 草苅伸也 他
  • Organizer: Neuro2013
  • Place of Presentation: 国立京都国際会館
• [Presentation] 細胞質型チロシンホスファターゼShp2の成熟脳における機能解析 (2013)
  • Author(s): 草苅伸也 他
  • Organizer: 第60回北関東医学会
  • Place of Presentation: 群馬大学
• [Presentation] チロシンホスファターゼShp2による脳機能・行動の制御
  • Author(s): 草苅伸也 他
  • Organizer: 第3回 群馬大学生体調節研究所内分泌・代謝学共同研究拠点シンポジウム
  • Place of Presentation: 群馬大学
• [Remarks] 群馬大学大学院保健学研究科大西研究室ホームページ
  • URL: http://biosignal.dept.med.gunma-u.ac.jp/index.php
• [Remarks] 群馬大学生体調節研究所ホームページ
  • URL: http://www.imcr.gunma-u.ac.jp/
• [Remarks] 研究室ホームページ
  • URL: http://biosignal.dept.med.gunma-u.ac.jp/index.php
• [Remarks] 所属機関ホームページ
  • URL: http://www.imcr.gunma-u.ac.jp/