Regulation of PirB, a functional receptor for axonal growth inhibitors, by LOTUS

• Project/Area Number: 26870480
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General pharmacology; Neurochemistry/Neuropharmacology
• Research Institution: Yokohama City University
• Principal Investigator: KURIHARA Yuji 横浜市立大学, 生命医科学研究科, 特任助教 (00634552)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 神経科学 / 神経再生阻害因子 / アンタゴニスト / 神経再生

Outline of Final Research Achievements

I analyzed the molecular and physiological function of LOTUS to paired immunoglobulin-like receptor B (PirB) which restricts functional recovery after damages to the central nervous system. I found that LOTUS interacted with PirB. LOTUS overexpressed with PirB in COS7 cells blocked the binding to PirB of Nogo, which is a functional ligand for PirB. Soluble form of LOTUS inhibited Nogo-induced growth cone collapse in cultured dorsal root ganglion neurons and Nogo-induced nerite outgrowth inhibition in cultured cerebellar granule neurons from ngr1-deficient mice. These data suggest that LOTUS functions as an antagonist for PirB.

Research Products

• [Journal Article] LOTUS, a potent blocker of Nogo receptor-1 causing inhibition of axonal growth. (2015)
  • Author(s): Kurihara Y, Takei K.
  • Journal Title: Neural Regen Res. Volume: 10 Issue: 1 Pages: 46-48
  • DOI: 10.4103/1673-5374.150652
  • Peer Reviewed / Open Access
• [Journal Article] Association of Cerebrospinal Fluid Levels of Lateral Olfactory Tract Usher Substance (LOTUS) With Disease Activity in Multiple Sclerosis (2015)
  • Author(s): Takahashi K, Kurihara Y, Suzuki Y, Goshima Y, Tanaka F, Takei K.
  • Journal Title: JAMA Neurol Volume: 72 Issue: 2 Pages: 176-179
  • DOI: 10.1001/jamaneurol.2014.3613
  • Peer Reviewed / Open Access
• [Journal Article] LOTUS suppresses axon growth inhibition by blocking interaction between Nogo receptor-1 and all four types of its ligand. (2014)
  • Author(s): Kurihara Y, Iketani M, Ito H, Nishiyama K, Sakakibara Y, Goshima Y, Takei K.
  • Journal Title: Molecular and Cellular Neuroscience Volume: 10 Pages: 211-218
  • DOI: 10.1016/j.mcn.2014.07.001
  • Peer Reviewed
• [Presentation] LOTUSはコンドロイチン硫酸プロテオグリカンにより誘起される軸索伸長阻害を抑制する. (2014)
  • Author(s): 栗原 裕司, 齋藤 優, 竹居 光太郎.
  • Organizer: 第37回日本神経科学大会
  • Place of Presentation: パシフィコ横浜（神奈川県）
  • Year and Date: 2014-09-13