2022 Fiscal Year Annual Research Report
Investigation of the role of radial glia in regulating LysoPtdGlc required for nervous system development
| Project/Area Number |
20K06884
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| Research Institution | Kyoto University |
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Principal Investigator |
GUY ADAM・TSUDA 京都大学, 生命科学研究科, 准教授 (30634779)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | Lipid biology / Developmental biology / Neuroscience / Neurochemistry / Cell biology |
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| Outline of Annual Research Achievements |
In this project, I made the discovery of two isomers of the axon guidance cue lysophosphatidylglucoside (LysoPtdGlc) that activate the orphan receptor GPR55 in a potentially novel mechanism. I found that LysoPtdGlc can exist in two biologically active isomeric forms, R-LysoPtdGlc and S-LysoPtdGlc, that are R/S stereoisomers. Whilst both isomers activate GPR55, R-LysoPtdGlc activates Galpha13 downstream of GPR55, whilst S-LysoPtdGlc activates GalphaS, and they induce polar-opposite chemotropic responses of axon growth. I confirmed this using drugs that specifically inhibit components of adenylyl cyclase pathway, and by specifically blocking different Galpha subunit pathways with inhibitory peptides. In summary, I have discovered a potential ligand bias or functional selectivity of GPR55.
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