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Activation of oligodendroglial Fyn kinase enhances translation of mRNAs transported in hnRNP A2–dependent RNA granules

Central nervous system myelination requires the synthesis of large amounts of myelin basic protein (MBP) at the axon–glia contact site. MBP messenger RNA (mRNA) is transported in RNA granules to oligodendroglial processes in a translationally silenced state. This process is regulated by the trans-ac...

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Autores principales: White, Robin, Gonsior, Constantin, Krämer-Albers, Eva-Maria, Stöhr, Nadine, Hüttelmaier, Stefan, Trotter, Jacqueline
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2386098/
https://www.ncbi.nlm.nih.gov/pubmed/18490510
http://dx.doi.org/10.1083/jcb.200706164
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author White, Robin
Gonsior, Constantin
Krämer-Albers, Eva-Maria
Stöhr, Nadine
Hüttelmaier, Stefan
Trotter, Jacqueline
author_facet White, Robin
Gonsior, Constantin
Krämer-Albers, Eva-Maria
Stöhr, Nadine
Hüttelmaier, Stefan
Trotter, Jacqueline
author_sort White, Robin
collection PubMed
description Central nervous system myelination requires the synthesis of large amounts of myelin basic protein (MBP) at the axon–glia contact site. MBP messenger RNA (mRNA) is transported in RNA granules to oligodendroglial processes in a translationally silenced state. This process is regulated by the trans-acting factor heterogeneous nuclear ribonucleoprotein (hnRNP) A2 binding to the cis-acting A2 response element (A2RE). Release of this repression of MBP mRNA translation is thus essential for myelination. Mice deficient in the Src family tyrosine kinase Fyn are hypomyelinated and contain reduced levels of MBP. Here, we identify hnRNP A2 as a target of activated Fyn in oligodendrocytes. We show that active Fyn phosphorylates hnRNP A2 and stimulates translation of an MBP A2RE–containing reporter construct. Neuronal adhesion molecule L1 binding to oligodendrocytes results in Fyn activation, which leads to an increase in hnRNP A2 phosphorylation. These results suggest that Fyn kinase activation results in the localized translation of MBP mRNA at sites of axon–glia contact and myelin deposition.
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spelling pubmed-23860982008-11-19 Activation of oligodendroglial Fyn kinase enhances translation of mRNAs transported in hnRNP A2–dependent RNA granules White, Robin Gonsior, Constantin Krämer-Albers, Eva-Maria Stöhr, Nadine Hüttelmaier, Stefan Trotter, Jacqueline J Cell Biol Research Articles Central nervous system myelination requires the synthesis of large amounts of myelin basic protein (MBP) at the axon–glia contact site. MBP messenger RNA (mRNA) is transported in RNA granules to oligodendroglial processes in a translationally silenced state. This process is regulated by the trans-acting factor heterogeneous nuclear ribonucleoprotein (hnRNP) A2 binding to the cis-acting A2 response element (A2RE). Release of this repression of MBP mRNA translation is thus essential for myelination. Mice deficient in the Src family tyrosine kinase Fyn are hypomyelinated and contain reduced levels of MBP. Here, we identify hnRNP A2 as a target of activated Fyn in oligodendrocytes. We show that active Fyn phosphorylates hnRNP A2 and stimulates translation of an MBP A2RE–containing reporter construct. Neuronal adhesion molecule L1 binding to oligodendrocytes results in Fyn activation, which leads to an increase in hnRNP A2 phosphorylation. These results suggest that Fyn kinase activation results in the localized translation of MBP mRNA at sites of axon–glia contact and myelin deposition. The Rockefeller University Press 2008-05-19 /pmc/articles/PMC2386098/ /pubmed/18490510 http://dx.doi.org/10.1083/jcb.200706164 Text en © 2008 White et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
White, Robin
Gonsior, Constantin
Krämer-Albers, Eva-Maria
Stöhr, Nadine
Hüttelmaier, Stefan
Trotter, Jacqueline
Activation of oligodendroglial Fyn kinase enhances translation of mRNAs transported in hnRNP A2–dependent RNA granules
title Activation of oligodendroglial Fyn kinase enhances translation of mRNAs transported in hnRNP A2–dependent RNA granules
title_full Activation of oligodendroglial Fyn kinase enhances translation of mRNAs transported in hnRNP A2–dependent RNA granules
title_fullStr Activation of oligodendroglial Fyn kinase enhances translation of mRNAs transported in hnRNP A2–dependent RNA granules
title_full_unstemmed Activation of oligodendroglial Fyn kinase enhances translation of mRNAs transported in hnRNP A2–dependent RNA granules
title_short Activation of oligodendroglial Fyn kinase enhances translation of mRNAs transported in hnRNP A2–dependent RNA granules
title_sort activation of oligodendroglial fyn kinase enhances translation of mrnas transported in hnrnp a2–dependent rna granules
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2386098/
https://www.ncbi.nlm.nih.gov/pubmed/18490510
http://dx.doi.org/10.1083/jcb.200706164
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