The oligodendrocyte-specific G protein-coupled receptor GPR17 is a cell-intrinsic timer of myelination

Ying Chen, Heng Wu, Shuzong Wang, Hisami Koito, Jianrong Li, Feng Ye, Jenny Hoang, Sabine S. Escobar, Alexander Gow, Heather A. Arnett, Bruce D. Trapp, Nitin J. Karandikar, Jenny Hsieh, Q. Richard Lu

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169 Scopus citations

Abstract

The basic helix-loop-helix transcription factor Olig1 promotes oligodendrocyte maturation and is required for myelin repair. We characterized an Olig1-regulated G protein-coupled receptor, GPR17, whose function is to oppose the action of Olig1. Gpr17 was restricted to oligodendrocyte lineage cells, but was downregulated during the peak period of myelination and in adulthood. Transgenic mice with sustained Gpr17 expression in oligodendrocytes exhibited stereotypic features of myelinating disorders in the CNS. Gpr17 overexpression inhibited oligodendrocyte differentiation and maturation both in vivo and in vitro. Conversely, Gpr17 knockout mice showed early onset of oligodendrocyte myelination. The opposing action of Gpr17 on oligodendrocyte maturation reflects, at least partially, upregulation and nuclear translocation of the potent oligodendrocyte differentiation inhibitors ID2/4. Collectively, these findings suggest that GPR17 orchestrates the transition between immature and myelinating oligodendrocytes via an ID protein-mediated negative regulation and may serve as a potential therapeutic target for CNS myelin repair.

Original languageEnglish (US)
Pages (from-to)1398-1406
Number of pages9
JournalNature neuroscience
Volume12
Issue number11
DOIs
StatePublished - Nov 1 2009

ASJC Scopus subject areas

  • Neuroscience(all)

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    Chen, Y., Wu, H., Wang, S., Koito, H., Li, J., Ye, F., Hoang, J., Escobar, S. S., Gow, A., Arnett, H. A., Trapp, B. D., Karandikar, N. J., Hsieh, J., & Lu, Q. R. (2009). The oligodendrocyte-specific G protein-coupled receptor GPR17 is a cell-intrinsic timer of myelination. Nature neuroscience, 12(11), 1398-1406. https://doi.org/10.1038/nn.2410