Molecular mechanism of proteolytic cleavage of Reelin

• Project/Area Number: 22890155
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Biological pharmacy
• Research Institution: Nagoya City University
• Principal Investigator: TAKAO Kohno 名古屋市立大学, 大学院・薬学研究科, 助教 (70581742)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,146,000 (Direct Cost: ¥2,420,000、Indirect Cost: ¥726,000); Fiscal Year 2011: ¥1,508,000 (Direct Cost: ¥1,160,000、Indirect Cost: ¥348,000); Fiscal Year 2010: ¥1,638,000 (Direct Cost: ¥1,260,000、Indirect Cost: ¥378,000)
• Keywords: 神経細胞 / 脳 / リーリン / プロテアーゼ / プロテオリシス / 神経回路

Research Abstract

Reelin is a large protein that is essential for brain development. Reelin is proteolytically cleaved at specific sites. In this study, we aimed to clarify the molecular mechanism of proteolytic cleavage of Reelin. We found following points.(1) Reelin does not have the proteolytic activity.(2) A disintegrin and metalloproteinase with thrombospondin motifs 4(ADAMTS-4) can cleave Reelin in an isoform-dependent manner.(3) Reelin with an intact CTR binds to a transmembrane protein that is different from the well-known Reelin receptors.

Research Products

• [Journal Article] Differential localization of sphingomyelin synthase isoforms in neurons regulates sphingomyelin cluster formation (2012)
  • Author(s): Kidani Y, Ohshima K, Sakai H, Kohno T, Baba A and Hattori M
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 417 Pages: 1014-1017
• [Journal Article] Differential localization of sphingomyelin synthase isoforms in neurons regulates sphingomyelin cluster formation (2012)
  • Author(s): Kidani Y., et al
  • Journal Title: Biochem Biophys Res Commun Volume: 417 Issue: 3 Pages: 1014-1017
  • DOI: 10.1016/j.bbrc.2011.12.079
  • Peer Reviewed
• [Journal Article] Functional importance of covalent homodimer of reelin protein linked via its central region (2011)
  • Author(s): Yasui N, Kitago Y, Beppu A, Kohno T, Morishita S, Gomi H, Nagae M, Hattori M and Takagi J
  • Journal Title: J. Biol. Chem Volume: 286 Pages: 35247-35256
• [Journal Article] Functional importance of covalent homodimer of reelin linked via its central region (2011)
  • Author(s): Yasui, N., et al.
  • Journal Title: J.Biol.Chem. Volume: 286 Issue: 40 Pages: 35247-35256
  • DOI: 10.1074/jbc.m111.242719
  • Peer Reviewed
• [Journal Article] Re-evaluation of protease activity of Reelin (2010)
  • Author(s): Kohno T, and Hattori M
  • Journal Title: Biol. Pharm. Bull Volume: 33 Pages: 1047-1049
• [Journal Article] 細胞外シグナル分子リーリンの分解機構と生理的意義 (2010)
  • Author(s): 河野孝夫、服部光治
  • Journal Title: 生化学 Volume: 82 Pages: 963-71
  • NAID: 10027502822
• [Journal Article] Re-evaluation of Protease Activity of Reelin (2010)
  • Author(s): Kohno T.
  • Journal Title: Biol Pharm Bull. Volume: 33 Pages: 1047-1049
  • Peer Reviewed
• [Journal Article] 細胞外シグナル分子リーリンの分解機構と生理的意義 (2010)
  • Author(s): 河野孝夫
  • Journal Title: 生化学 Volume: 82 Pages: 963-971
  • NAID: 10027502822
• [Presentation] 脳形成に必須な分泌蛋白質リーリンの、新規分解機構とその生理的意義 (2012)
  • Author(s): 河野孝夫、土屋綾香、服部光治
  • Organizer: 日本薬学会第132年会
  • Year and Date: 2012-03-29
• [Presentation] 脳形成に必須な分泌タンパク質リーリンの特異的切断へのADAMTSの関与 (2012)
  • Author(s): 森下駿介、久永有紗、河野孝夫、服部光治
  • Organizer: 日本薬学会第132年会
  • Year and Date: 2012-03-29
• [Presentation] 難読症関連遺伝子KIAA0319の神経細胞突起形成における機能解明 (2012)
  • Author(s): 山本恭平、田頭大志、鈴木友美子、河野孝夫、服部光治
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 北海道大学
  • Year and Date: 2012-03-29
• [Presentation] Mechanism of specific proteolytic cleavage of Reelin (2011)
  • Author(s): Kidani Y, Koie M, Hisanaga A, Kohno T and Hattori M
  • Organizer: Neuroscience2011
  • Year and Date: 2011-11-16
• [Presentation] Mechanism of specific proteolytic cleavage of Reelin (2011)
  • Author(s): Kidani Y., Koie M., Hisanaga A., Kohno T., Hattori M.
  • Organizer: Neuroscience2011-Society for Neuroscience
  • Place of Presentation: Washington D.C.
  • Year and Date: 2011-11-16
• [Presentation] Interaction between the dyslexia-associated protein KIAA0319 and radixin regulates (2011)
  • Author(s): Tagashira M., Sugie M., Kidani Y., Kohno T., Hattori M.
  • Organizer: Neuroscience2011-Society for Neuroscience
  • Place of Presentation: Washington D.C.
  • Year and Date: 2011-11-16
• [Presentation] 難読症関連遺伝子産物KIAA0319とEphファミリーとの結合意義の解明 (2011)
  • Author(s): 杉江真梨子、深見瑛、河野孝夫、服部光治
  • Organizer: 日本薬学会第83会日本生化学会大会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2011-09-23
• [Presentation] Molecular mechanism of proteolytic cleavage of Reelin (2011)
  • Author(s): 佐々木一友、鈴木健太、鯉江真利、久永有紗、河野孝夫、服部光治
  • Organizer: 日本薬学会第83会日本生化学会大会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2011-09-23
• [Presentation] Proteolytic cleavage of Reelin within its C-terminal region regulates its ability to induce growth cone collapse (2011)
  • Author(s): Kohno T, Tsuchiya A, Matsumaru S, Takayanagi M and Hattori M
  • Organizer: 第34回日本神経科学大会
  • Year and Date: 2011-09-16
• [Presentation] Proteolytic cleavage of Reelin within its C-terminal region regulates its ability to induce growth cone collapse (2011)
  • Author(s): Kohno T., Tsuchiya A., Matsumaru S., Takayanagi M., Hattori M.
  • 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: 2011-09-16
• [Presentation] The functions of c-terminal region of Reelin in cerebral cortex : the neuronal layer maintenance and astrocytegenesis (2011)
  • Author(s): Murakami T., Kohno T., Banno H., Nakano Y., Hattori M.
  • 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: 2011-09-16
• [Presentation] Mechanism of cerebellar development as revealed by Reelin CTR-deficient mouse (2011)
  • Author(s): Nakamura K., Banno H., Nakano Y., Kohno T., Hattori M.
  • 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: 2011-09-16
• [Presentation] 脳形成に必須な巨大分泌蛋白質リーリンの特異的分解を担うプロテアーゼに関する解析 (2011)
  • Author(s): 河野孝夫、久永有紗、鈴木健太、鯉江真利、服部光治
  • Organizer: 第16回日本病態プロテアーゼ学会学術集会
  • Year and Date: 2011-08-26
• [Presentation] リーリンおよびリーリン受容体の細胞内動態とその生理的意義の解明 (2011)
  • Author(s): 〓夢妍
  • Organizer: 日本薬学会 第131年会
  • Place of Presentation: ツインメッセ静岡(静岡県)
  • Year and Date: 2011-03-30
• [Presentation] 脳形成に必須な分泌タンパク質リーリンの特異的切断を担うプロテアーゼに関する解析 (2011)
  • Author(s): 久永有紗
  • Organizer: 日本薬学会 第131年会
  • Place of Presentation: ツインメッセ静岡(静岡県)
  • Year and Date: 2011-03-30
• [Presentation] Mechanism of specific proteolytic cleavage of Reelin (2010)
  • Author(s): Suzuki K, Kohno S, Koie M, Kohno T and Hattori M
  • Organizer: BMB2010
  • Year and Date: 2010-12-07
• [Presentation] リーリンの機能調節における、C末端領域の生理的意義 (2010)
  • Author(s): 河野孝夫
  • Organizer: BMB2010
  • Place of Presentation: 神戸ポートアイランド(兵庫県)
  • Year and Date: 2010-12-07
• [Presentation] モノクローナル抗体を用いた、リーリンの時空間的作用点の解明 (2010)
  • Author(s): 中川裕介
  • Organizer: BMB2010
  • Place of Presentation: 神戸ポートアイランド(兵庫県)
  • Year and Date: 2010-12-07
• [Presentation] リーリンN末端領域の機能解明 (2010)
  • Author(s): 五味宏樹
  • Organizer: BMB2010
  • Place of Presentation: 神戸ポートアイランド(兵庫県)
  • Year and Date: 2010-12-07
• [Presentation] リーリンの特異的切断機構の解明 (2010)
  • Author(s): 鈴木健太
  • Organizer: BMB2010
  • Place of Presentation: 神戸ポートアイランド(兵庫県)
  • Year and Date: 2010-12-07
• [Presentation] リーリンC末端領域の機能解明 (2010)
  • Author(s): 河野孝夫
  • Organizer: Neuro2010
  • Place of Presentation: 神戸コンベンションセンター(兵庫県)
  • Year and Date: 2010-09-02
• [Remarks]
  • URL: http://www.phar.nagoya-cu.ac.jp/hp/bsk/indexj1.html
• [Patent(Industrial Property Rights)] 抗体とその利用 (2011)
  • Inventor(s): 服部光治、河野孝夫、鯉江真利、久永有紗
  • Industrial Property Rights Holder: 名古屋市立大学
  • Industrial Property Number: 2011-179161
  • Filing Date: 2011-08-18