Structural and functional analyses of voltage-gated sodium channel beta subunits

• Project/Area Number: 24770195
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cell biology
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: SHIMIZU Hideaki 独立行政法人理化学研究所, ライフサイエンス技術基盤研究センター, 研究員 (10360562)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 電位依存性ナトリウムチャネルβサブユニット / 電位依存性ナトリウムチャネル / βサブユニット / 細胞接着 / 結晶構造解析 / 細胞間相互作用 / 結晶構造 / GEFS+

Outline of Final Research Achievements

The voltage-gated sodium channel β subunits (β1-β4, encoded by SCN1B-4B, respectively) reportedly function as cell adhesion molecules. A genetic epilepsy syndrome, generalized epilepsy with febrile seizures plus　(GEFS+), has been correlated directly with mutations in SCN1B, encoding β1, suggesting a potential causal relationship between cell-cell adhesion and GEFS+ pathogenesis. In this study, we identified the relationship between the structural feature and cell-cell adhesion of beta subunits. In addition, we found that the GEFS+ mutations could disrupt the trans-homophilic interaction in cell-cell adhesion.

Research Products

• [Journal Article] Singular localization of sodium channel β4 subunit in unmyelinated fibres and its role in the striatum. (2014)
  • Author(s): Miyazaki H, Oyama F, Inoue R, Aosaki T, Abe T, Kiyonari H, Kino Y, Kurosawa M, Shimizu J, Ogiwara I, Yamakawa K, Koshimizu Y, Fujiyama F, Kaneko T, Shimizu H, Nagatomo K, Yamada K, Shimogori T, Hattori N, Miura M, Nukina N.
  • Journal Title: Nat Commun. Volume: 5 Issue: 1 Pages: 5525-5525
  • DOI: 10.1038/ncomms6525
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Structural basis for the trans- and cis-interactions of the voltage-gated sodium channel β subunits (2014)
  • Author(s): 清水 英明、 白水 美香子、 貫名 信行、関根 俊一、横山 茂之
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-11-25
• [Presentation] Structural basis for the trans- and cis-interactions of the voltage-gated sodium channel β subunits (2014)
  • Author(s): 清水 英明、 白水 美香子、 貫名 信行、関根 俊一、横山 茂之
  • 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: 2014-09-13
• [Presentation] Structural basis of the functional interaction in voltage-gated sodium channel beta subunit and implications for pathogenic mechanism of epilepsy (2012)
  • Author(s): Hideaki Shimizu, Haruko Miyazaki, Mikako Shirouzu, Nobuyuki Nukina, Shigeyuki Yokoyama
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
• [Presentation] Structural and functional analysis of voltage-gated sodium channel beta-subunit and epilepsy-causing mutation (2012)
  • Author(s): Hideaki Shimizu, Haruko Miyazaki, Shisako Shoji, Mikako Shirouzu, Nobuyuki Nukina, Shigeyuki Yokoyama
  • Organizer: 第35回日本神経科学大会
  • Place of Presentation: 名古屋