• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

First neuronal guidance lipid: Elucidation of biosynthesis and development of lead compounds to support neuronal recovery after injury

Research Project

Project/Area Number 16K08259
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Biological pharmacy
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Greimel Peter  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, 専任研究員 (60525541)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsPhosphatidylglucoside / GPCR / Lipids / GPR55 / GPRC / Biosynthesis / lipid-biosynthesis
Outline of Final Research Achievements

To characterize lysolipid-GPR55 interaction a novel homology model of GPR55 was created. Synthetic access to LysoPtdGlc and selected analogues featuring modifications on the acyl chain and on the phosphate moiety were established. The biological activity of each synthetic lipid was assessed using a GPR55-dependent chemotropism assay in primary sensory neurons. Molecular dynamics simulations of the GPR55 homology model in presence of synthetic lysolipid ligands have been performed and assessed. Combination of the molecular dynamics simulations and biological experiments provided insight into the potential ligand entry port and binding pocket specifics of GPR55. These results highlight the preference for gluco- over inositol- and galacto-configured headgroups. Furthermore, the specific acyl chain length required for GPR55 activation has been determined and is in good agreement with the created homology model of GPR55.

Academic Significance and Societal Importance of the Research Achievements

Detailed characterization of the GPR55 ligand binding pocket is an essential per-requisite for rational design of novel GPR55 specific antagonists, which have a high potential to be applied in neuropathic pain relieve treatments in the future.

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (13 results)

All 2019 2018 2017 2016

All Journal Article (8 results) (of which Int'l Joint Research: 8 results,  Peer Reviewed: 8 results,  Open Access: 3 results) Presentation (4 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results) Funded Workshop (1 results)

  • [Journal Article] Formation of tubules and helical ribbons by ceramide phosphoethanolamine-containing membranes.2019

    • Author(s)
      Inaba T., Murate M., Tomishige N., Lee Y.-F., Hullin-Matsuda F., Pollet B., Humbert N., Mely Y., Sako Y., Greimel P. and Kobayashi T.
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 5812-5812

    • DOI

      10.1038/s41598-019-42247-1

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Biophysical Properties of Phosphtidylglucoside and Phosphatidylinositol: Specific Differences in Head Group Interaction2018

    • Author(s)
      Greimel Peter
    • Journal Title

      Trends in Glycoscience and Glycotechnology

      Volume: 30 Issue: 171 Pages: E1-E13

    • DOI

      10.4052/tigg.1704.1E

    • NAID

      130006319125

    • ISSN
      0915-7352, 1883-2113
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Squaryl group modified phosphoglycolipid analogs as potential modulators of GPR552018

    • Author(s)
      Ding Feiqing、Guy Adam T.、Greimel Peter、Hirabayashi Yoshio、Kamiguchi Hiroyuki、Ito Yukishige
    • Journal Title

      Chemical Communications

      Volume: 54 Issue: 61 Pages: 8470-8473

    • DOI

      10.1039/c8cc04467h

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] GPRC5B-Mediated Sphingomyelin Synthase 2 Phosphorylation Plays a Critical Role in Insulin Resistance2018

    • Author(s)
      Kim Yeon-Jeong、Greimel Peter、Hirabayashi Yoshio
    • Journal Title

      iScience

      Volume: 8 Pages: 250-266

    • DOI

      10.1016/j.isci.2018.10.001

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Preference for Glucose over Inositol Headgroup during Lysolipid Activation of G Protein-Coupled Receptor 552018

    • 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

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Eudicot plant-specific sphingolipids determine host selectivity of microbial NLP cytolysins2017

    • Author(s)
      Lenarcic T., Albert I.、Boehm H.、Hodnik V.、Pirc K.、Zavec A. B.、Podobnik M.、Pahovnik D.、Zagar E.a、Pruitt R.、Greimel P.、Yamaji-Hasegawa A.、Kobayashi T.、Zienkiewicz A.、Goemann J.、Mortimer J. C.、Fang L.、Mamode-Cassim A.、Deleu M.、Lins L.、Oecking C.、Feussner I.、Mongrand S.、Anderluh G.、Nuernberger T.
    • Journal Title

      Science

      Volume: 358 Issue: 6369 Pages: 1431-1434

    • DOI

      10.1126/science.aan6874

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Photoswitchable phospholipid FRET acceptor: Detergent free intermembrane transfer assay of fluorescent lipid analogs2017

    • Author(s)
      Sumi Mariko、Makino Asami、Inaba Takehiko、Sako Yasushi、Fujimori Fumihiro、Greimel Peter、Kobayashi Toshihide
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 1-10

    • DOI

      10.1038/s41598-017-02980-x

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A novel spingomyeling/cholesterol specific probe reveals the dynamics of the membrane domain during virus and in Nieman-Pick type C2016

    • Author(s)
      Makino, A., Sako, Y. et al.
    • Journal Title

      FASEB J.

      Volume: 31 Issue: 4 Pages: 1301-1322

    • DOI

      10.1096/fj.201500075r

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Phosphatidyl-β-D-glucoside: From Biosynthesis to Biological Activity of Synthetic Analogues2018

    • Author(s)
      P. Greimel, A.T. Guy, H.H. Hung, Y. Nagatsuka, I. Matsuo, Y. Ito, H. Kamiguchi, Y. Hirabayashi
    • Organizer
      29th International Carbohydrate Conference
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] GPR55 Ligands: From Endocanabinoids to Lysolipids2018

    • Author(s)
      Greimel Peter
    • Organizer
      RIKEN Symposium, Wako, Japan
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Probing Lipid-Cholesterol Interaction2017

    • Author(s)
      Greimel Peter
    • Organizer
      International Membrane Seminar, Osaka, Japan
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Lyso-Phosphatidyl-β-D-glucoside Analogues as GPR55 Agonists: Synthesis and Modality-Specific Repulsive Guidance of Nociceptive Neurons2017

    • Author(s)
      Adam T. Guy, Yukishige Ito, Hiroyuki Kamiguchi, Yoshio Hirabayashi, Peter Greimel
    • Organizer
      19th European Carbohydrate Symposium; EUROCARB2017
    • Related Report
      2017 Research-status Report
  • [Funded Workshop] 57th International Conference on the Bioscience of Lipids2016

    • Place of Presentation
      France
    • Year and Date
      2016-09-04
    • Related Report
      2016 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi