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The oligodendrocyte-enriched orphan G protein-coupled receptor Gpr62 is dispensable for central nervous system myelination

BACKGROUND: Myelination is a highly regulated process in the vertebrate central nervous system (CNS) whereby oligodendrocytes wrap axons with multiple layers of insulating myelin in order to allow rapid electrical conduction. Establishing the proper pattern of myelin in neural circuits requires comm...

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Autores principales: Hay, Curtis M., Jackson, Stacey, Mitew, Stanislaw, Scott, Daniel J., Koenning, Matthias, Bensen, AeSoon L., Bujalka, Helena, Kilpatrick, Trevor J., Emery, Ben
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8630896/
https://www.ncbi.nlm.nih.gov/pubmed/34844642
http://dx.doi.org/10.1186/s13064-021-00156-y
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author Hay, Curtis M.
Jackson, Stacey
Mitew, Stanislaw
Scott, Daniel J.
Koenning, Matthias
Bensen, AeSoon L.
Bujalka, Helena
Kilpatrick, Trevor J.
Emery, Ben
author_facet Hay, Curtis M.
Jackson, Stacey
Mitew, Stanislaw
Scott, Daniel J.
Koenning, Matthias
Bensen, AeSoon L.
Bujalka, Helena
Kilpatrick, Trevor J.
Emery, Ben
author_sort Hay, Curtis M.
collection PubMed
description BACKGROUND: Myelination is a highly regulated process in the vertebrate central nervous system (CNS) whereby oligodendrocytes wrap axons with multiple layers of insulating myelin in order to allow rapid electrical conduction. Establishing the proper pattern of myelin in neural circuits requires communicative axo-glial interactions, however, the molecular interactions that occur between oligodendrocytes and axons during developmental myelination and myelin maintenance remain to be fully elucidated. Our previous work identified G protein-coupled receptor 62 (Gpr62), an uncharacterized orphan g-protein coupled receptor, as being selectively expressed by mature oligodendrocytes within the CNS, suggesting a potential role in myelination or axoglial interactions. However, no studies to date have assessed the functional requirement for Gpr62 in oligodendrocyte development or CNS myelination. METHODS: To address this, we generated a knockout mouse strain lacking the Gpr62 gene. We assessed CNS myelination during both postnatal development and adulthood using immunohistochemistry, electron microscopy and western blot. In addition, we utilized AAV-mediated expression of a tagged Gpr62 in oligodendrocytes to determine the subcellular localization of the protein in vivo. RESULTS: We find that virally expressed Gpr62 protein is selectively expressed on the adaxonal myelin layer, suggestive of a potential role for Gpr62 in axo-myelinic signaling. Nevertheless, Gpr62 knockout mice display normal oligodendrocyte numbers and apparently normal myelination within the CNS during both postnatal development and adulthood. CONCLUSIONS: We conclude that in spite of being well-placed to mediate neuronal-oligodendrocyte communications, Gpr62 is overall dispensable for CNS myelination.
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spelling pubmed-86308962021-12-01 The oligodendrocyte-enriched orphan G protein-coupled receptor Gpr62 is dispensable for central nervous system myelination Hay, Curtis M. Jackson, Stacey Mitew, Stanislaw Scott, Daniel J. Koenning, Matthias Bensen, AeSoon L. Bujalka, Helena Kilpatrick, Trevor J. Emery, Ben Neural Dev Research Article BACKGROUND: Myelination is a highly regulated process in the vertebrate central nervous system (CNS) whereby oligodendrocytes wrap axons with multiple layers of insulating myelin in order to allow rapid electrical conduction. Establishing the proper pattern of myelin in neural circuits requires communicative axo-glial interactions, however, the molecular interactions that occur between oligodendrocytes and axons during developmental myelination and myelin maintenance remain to be fully elucidated. Our previous work identified G protein-coupled receptor 62 (Gpr62), an uncharacterized orphan g-protein coupled receptor, as being selectively expressed by mature oligodendrocytes within the CNS, suggesting a potential role in myelination or axoglial interactions. However, no studies to date have assessed the functional requirement for Gpr62 in oligodendrocyte development or CNS myelination. METHODS: To address this, we generated a knockout mouse strain lacking the Gpr62 gene. We assessed CNS myelination during both postnatal development and adulthood using immunohistochemistry, electron microscopy and western blot. In addition, we utilized AAV-mediated expression of a tagged Gpr62 in oligodendrocytes to determine the subcellular localization of the protein in vivo. RESULTS: We find that virally expressed Gpr62 protein is selectively expressed on the adaxonal myelin layer, suggestive of a potential role for Gpr62 in axo-myelinic signaling. Nevertheless, Gpr62 knockout mice display normal oligodendrocyte numbers and apparently normal myelination within the CNS during both postnatal development and adulthood. CONCLUSIONS: We conclude that in spite of being well-placed to mediate neuronal-oligodendrocyte communications, Gpr62 is overall dispensable for CNS myelination. BioMed Central 2021-11-29 /pmc/articles/PMC8630896/ /pubmed/34844642 http://dx.doi.org/10.1186/s13064-021-00156-y Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Hay, Curtis M.
Jackson, Stacey
Mitew, Stanislaw
Scott, Daniel J.
Koenning, Matthias
Bensen, AeSoon L.
Bujalka, Helena
Kilpatrick, Trevor J.
Emery, Ben
The oligodendrocyte-enriched orphan G protein-coupled receptor Gpr62 is dispensable for central nervous system myelination
title The oligodendrocyte-enriched orphan G protein-coupled receptor Gpr62 is dispensable for central nervous system myelination
title_full The oligodendrocyte-enriched orphan G protein-coupled receptor Gpr62 is dispensable for central nervous system myelination
title_fullStr The oligodendrocyte-enriched orphan G protein-coupled receptor Gpr62 is dispensable for central nervous system myelination
title_full_unstemmed The oligodendrocyte-enriched orphan G protein-coupled receptor Gpr62 is dispensable for central nervous system myelination
title_short The oligodendrocyte-enriched orphan G protein-coupled receptor Gpr62 is dispensable for central nervous system myelination
title_sort oligodendrocyte-enriched orphan g protein-coupled receptor gpr62 is dispensable for central nervous system myelination
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8630896/
https://www.ncbi.nlm.nih.gov/pubmed/34844642
http://dx.doi.org/10.1186/s13064-021-00156-y
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