Mechanism and physiological role for generation of the carboxyl terminal fragment of the P/Q-type calcium channel

2011 Fiscal Year Final Research Report

• Project/Area Number: 21590228
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General physiology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: SAEGUSA Hironao 東京医科歯科大学, 大学院・医歯学総合研究科, 助教 (90261205)
• Project Period (FY): 2009 – 2011
• Keywords: Cav2. 1,カルボキシ末端 / プロテアーゼ / 脊髄小脳変性症6型 / SCA6

Research Abstract

Generation of Cav2. 1 carboxyl terminal tail(Cav2. 1CT) is thought to be causally related to spinocerebellar ataxia type 6, a hereditary neurological disease. Cav2. 1CT is generated by cleavage of the full-length Cav2. 1 protein. But the exact mechanism underlying the generation of Cav2. 1CT and the function of this CT fragment remain to be clarified. In the present study, I have tried to clarify the mechanism to generate the Cav2. 1CT from full-length Cav2. 1 protein. Also, I have studied the functional role of the Cav2. 1CT in some in vitro systems. As a result, the following molecules are candidates for the protease responsible for the Cav2. 1CT generation : caspase 6, cathepsin L, and calpain small subunit 1, but further studies are necessary to conclude this. Cav2. 1CT was found to be toxic to cells and it is possible that Cav2. 1CT possess transcription repressing activity

Research Products

• [Journal Article] Upregulation of casein kinase 1epsilon in dorsal root ganglia and spinal cord after mouse spinal nerve injury contributes to neuropathic pain (2009)
  • Author(s): Sakurai, E., Kurihara, T., Kouchi, K., Saegusa, H., Zong, S. and Tanabe, T
  • Journal Title: Molecular Pain Volume: 5 Pages: 74
  • Peer Reviewed
• [Journal Article] Deficit of heat shock transcription factor 1-heat shock 70 kDa protein 1A axis determines the cell death vulnerability in a model of spinocerebellar ataxia type 6 (2009)
  • Author(s): Li, L., Saegusa, H. and Tanabe, T
  • Journal Title: Genes to Cells Volume: 14 Pages: 1253-1269
  • Peer Reviewed
• [Journal Article] Peripheral-type benzodiazepine receptor antagonist is effective in relieving neuropathic pain in mice (2009)
  • Author(s): Kondo, D., Saegusa, H., Yabe, R., Takasaki, I., Kurihara, T., Zong, S. and Tanabe, T
  • Journal Title: Journal of Pharmacological Science Volume: 110 Pages: 55-63
  • Peer Reviewed
• [Presentation] Down regulation of particular miRNAs is responsible for the cell death vulnerability of Spinocerebellar ataxia type 6(SCA6) (2011)
  • Author(s): Tanabe, T, et al.
  • Organizer: The 41st annual meeting of the Society for Neuroscience
  • Place of Presentation: Washington DC, USA
  • Year and Date: 20111112-16
• [Presentation] Involvement of miRNA in the pathogenesis of Spinocerebellar ataxia type 6(SCA6) (2011)
  • Author(s): Tanabe T, et al.
  • Organizer: 8th IBRO World Congress of Neuroscience
  • Place of Presentation: Florence, Italy
  • Year and Date: 20110714-18
• [Presentation] Down-regulation of heat shock transcription factor 1-heat shock 70kDa protein 1A axis and increased caspase-dependent apoptosis in a cell model of spinocerebellar ataxia type 6(SCA6) (2009)
  • Author(s): Li L, et al.
  • Organizer: 日本分子生物学会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2009-12-09
• [Remarks]
  • URL: http://www.tmd.ac.jp/med/mphm/Yakuri.HTM