2022 Fiscal Year Final 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 Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 46010:Neuroscience-general-related
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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 / Molecular biology / Cell biology |
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| Outline of Final Research Achievements |
I previously found that lysophosphatidylglucoside (LysoPtdGlc) is a lipid axon guidance cue required for the development of nociceptive axon circuits in spinal cord. In this project, I have discovered that radial glial LysoPtdGlc can exist in two isomeric forms, R-LysoPtdGlc and S-LysoPtdGlc. I found that whilst both R- and S-forms activate the orphan receptor GPR55, they signal via different downstream intracellular cascades: R-LysoPtdGlc induces Galpha13 activation, whilst S-LysoPtdGlc activates GalphaS. In an assay of axon chemotropism, I discovered that the two isomers, although they both activate GPR55, induce cellular chemotropic response of opposite polarity: R-form induces chemorepulsion, S-form induces chemoattraction, strongly suggesting a mechanism of functional selectivity or ligand bias at GPR55. Neither form induces a response in neurons genetically lacking GPR55. I have also obtained preliminary data for R- and S-forms in an in vivo model of mouse neuropathic pain.
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| Free Research Field |
Developmental neurobiology
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| Academic Significance and Societal Importance of the Research Achievements |
I determined that the axon guidance cue LysoPtdGlc can exist as one of two biologically active isomers: R-LysoPtdGlc and S-LysoPtdGlc. I found that downstream of GPR55, R-LysoPtdGlc activates Galpha13 whilst S-LysoPtdGlc activates GalphaS, strongly suggesting that they are biased ligands of GPR55.
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