| 研究実績の概要 |
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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