Identification and characterization of PLA2 enzyme required for sensory nervous system development

• Project/Area Number: 17K14970
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Guy Adam Tsuda 国立研究開発法人理化学研究所, 脳神経科学研究センター, 研究員 (30634779)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: Lipid biology / Neuroscience / Developmental biology / Molecular biology / Cell biology / Lipid Biology / Cell Biology / Molecular Biology / 神経科学 / 脳・神経 / 脂質 / 発生・分化

Outline of Final Research Achievements

Axon guidance cues are signaling molecules that instruct growing axons to form the correct connections within the developing nervous system. I previously have determined that lysophosphatidylglucoside is an axon guidance cue required for the development of nociceptive (pain-sensing) axon circuits in the spinal cord. In this project I have discovered that radial glia, the progenitor cells in the nervous system, possess an enzyme called secreted phospholipase A2 (sPLA2), specific isoform V, which produces lysophosphatidylglucoside (LysoPtdGlc). Spinal cords that lack the gene for sPLA2 V develop nociceptive axons in the wrong position. Therefore, radial glial sPLA2 V is required for correct nociceptive axon tract formation.

Academic Significance and Societal Importance of the Research Achievements

I determined that a single isoform of secreted PLA2 enzyme, sPLA2 V, is required for normal embryonic development of nociceptive axon tracts in spinal cord. sPLA2/LysoPtdGlc-signaling is required for normal nociception, therefore this mechanism may play a role in disorders such as neuropathic pain.

Research Products

• [Journal Article] Preference for Glucose over Inositol Headgroup during Lysolipid Activation of G Protein-Coupled Receptor 55 (2018)
  • Author(s): Guy Adam T.、Kano Koki、Ohyama Jyunpei、Kamiguchi Hiroyuki、Hirabayashi Yoshio、Ito Yukishige、Matsuo Ichiro、Greimel Peter
  • Journal Title: ACS Chemical Neuroscience Volume: 10 Issue: 1 Pages: 716-727
  • DOI: 10.1021/acschemneuro.8b00505
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Identification of phospholipase A2 enzymes required for LysoPtdGlc/GPR55-mediated nociceptive circuit development (2019)
  • Author(s): Adam T. Guy
  • Organizer: Japan Neuroscience Society Meeting Neuro2019
• [Presentation] Functional analyses of cell signaling mediated by lysophosphatidylglucoside (2019)
  • Author(s): Adam T. Guy
  • Organizer: RIKEN Symposium Chemical Biology of Intracellular Glycan Modification
  • Invited
• [Presentation] Role of phospholipase A2 enzymes in LysoPtdGlc/GPR55-mediated axon guidance of nociceptive sensory afferents in developing spinal cord (2018)
  • Author(s): Guy AT, Inoue M, Greimel P, Yamamoto K, Hirabayashi Y, Murakami M, Kamiguchi H
  • Organizer: Cold Spring Harbor Laboratory meeting "Molecular Mechanisms of Neuronal Connectivity"
  • Int'l Joint Research
• [Presentation] Role of phospholipase A2 enzymes in nociceptive sensory afferent projection in spinal cord development (2017)
  • Author(s): Guy AT, Inoue M, Greimel P, Yamamoto K, Hirabayashi Y, Murakami M, Kamiguchi H
  • Organizer: MRC Centre for Neurodevelopmental Disorders Symposium "The Developing Brain in Health and Disease"