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

doi:10.1038/nn.2410

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

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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, …

Nature neuroscience, Vol.12(11), pp.1398-1406

11/2009

DOI: 10.1038/nn.2410

PMCID: PMC2783566

PMID: 19838178

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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.

Stem Cells

Optic Nerve - cytology

Embryo, Mammalian

Humans

Nerve Tissue Proteins - deficiency

Rats, Inbred F344

Green Fluorescent Proteins - genetics

Demyelinating Diseases - metabolism

Transfection - methods

Time Factors

Chromatin Immunoprecipitation - methods

Female

Spinal Cord - cytology

Disease Models, Animal

Multiple Sclerosis - metabolism

Receptors, G-Protein-Coupled - physiology

Demyelinating Diseases - physiopathology

Brain - cytology

Encephalomyelitis, Autoimmune, Experimental - physiopathology

Nerve Tissue Proteins - physiology

Encephalomyelitis, Autoimmune, Experimental - pathology

Mice, Inbred C57BL

Cells, Cultured

Rats

Mice, Transgenic

Multiple Sclerosis - genetics

Animals

Receptors, G-Protein-Coupled - deficiency

Multiple Sclerosis - pathology

Oligodendroglia

Mice

Details

Title: Subtitle: The oligodendrocyte-specific G protein-coupled receptor GPR17 is a cell-intrinsic timer of myelination
Creators: Ying Chen - Department of Developmental Biology and Kent Waldrep Foundation Center for Basic Neuroscience Research on Nerve Growth and Regeneration, University of Texas Southwestern Medical Center, Dallas, Texas, USA
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
Resource Type: Journal article
Publication Details: Nature neuroscience, Vol.12(11), pp.1398-1406
DOI: 10.1038/nn.2410
PMID: 19838178
PMCID: PMC2783566
NLM abbreviation: Nat Neurosci
ISSN: 1097-6256
eISSN: 1546-1726
Publisher: United States
Grant note: R01 NS060017-02 / NINDS NIH HHS R01 NS060017-04 / NINDS NIH HHS K24 AI079272-02 / NIAID NIH HHS K24 AI079272-01A1 / NIAID NIH HHS R01 NS060017-01A1 / NINDS NIH HHS R01 NS060017-03 / NINDS NIH HHS R01 NS050389-05 / NINDS NIH HHS R01 NS050389 / NINDS NIH HHS K24 AI079272 / NIAID NIH HHS R01 NS060017 / NINDS NIH HHS
Language: English
Date published: 11/2009
Academic Unit: Pathology
Record Identifier: 9984046808602771

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