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Involvement of the Tyro3 receptor and its intracellular partner Fyn signaling in Schwann cell myelination
During early development of the peripheral nervous system, Schwann cell precursors proliferate, migrate, and differentiate into premyelinating Schwann cells. After birth, Schwann cells envelop neuronal axons with myelin sheaths. Although some molecular mechanisms underlying myelination by Schwann ce...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4591693/ https://www.ncbi.nlm.nih.gov/pubmed/26224309 http://dx.doi.org/10.1091/mbc.E14-05-1020 |
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author | Miyamoto, Yuki Torii, Tomohiro Takada, Shuji Ohno, Nobuhiko Saitoh, Yurika Nakamura, Kazuaki Ito, Akihito Ogata, Toru Terada, Nobuo Tanoue, Akito Yamauchi, Junji |
author_facet | Miyamoto, Yuki Torii, Tomohiro Takada, Shuji Ohno, Nobuhiko Saitoh, Yurika Nakamura, Kazuaki Ito, Akihito Ogata, Toru Terada, Nobuo Tanoue, Akito Yamauchi, Junji |
author_sort | Miyamoto, Yuki |
collection | PubMed |
description | During early development of the peripheral nervous system, Schwann cell precursors proliferate, migrate, and differentiate into premyelinating Schwann cells. After birth, Schwann cells envelop neuronal axons with myelin sheaths. Although some molecular mechanisms underlying myelination by Schwann cells have been identified, the whole picture remains unclear. Here we show that signaling through Tyro3 receptor tyrosine kinase and its binding partner, Fyn nonreceptor cytoplasmic tyrosine kinase, is involved in myelination by Schwann cells. Impaired formation of myelin segments is observed in Schwann cell neuronal cultures established from Tyro3-knockout mouse dorsal root ganglia (DRG). Indeed, Tyro3-knockout mice exhibit reduced myelin thickness. By affinity chromatography, Fyn was identified as the binding partner of the Tyro3 intracellular domain, and activity of Fyn is down-regulated in Tyro3-knockout mice, suggesting that Tyro3, acting through Fyn, regulates myelination. Ablating Fyn in mice results in reduced myelin thickness. Decreased myelin formation is observed in cultures established from Fyn-knockout mouse DRG. Furthermore, decreased kinase activity levels and altered expression of myelination-associated transcription factors are observed in these knockout mice. These results suggest the involvement of Tyro3 receptor and its binding partner Fyn in Schwann cell myelination. This constitutes a newly recognized receptor-linked signaling mechanism that can control Schwann cell myelination. |
format | Online Article Text |
id | pubmed-4591693 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-45916932015-12-16 Involvement of the Tyro3 receptor and its intracellular partner Fyn signaling in Schwann cell myelination Miyamoto, Yuki Torii, Tomohiro Takada, Shuji Ohno, Nobuhiko Saitoh, Yurika Nakamura, Kazuaki Ito, Akihito Ogata, Toru Terada, Nobuo Tanoue, Akito Yamauchi, Junji Mol Biol Cell Articles During early development of the peripheral nervous system, Schwann cell precursors proliferate, migrate, and differentiate into premyelinating Schwann cells. After birth, Schwann cells envelop neuronal axons with myelin sheaths. Although some molecular mechanisms underlying myelination by Schwann cells have been identified, the whole picture remains unclear. Here we show that signaling through Tyro3 receptor tyrosine kinase and its binding partner, Fyn nonreceptor cytoplasmic tyrosine kinase, is involved in myelination by Schwann cells. Impaired formation of myelin segments is observed in Schwann cell neuronal cultures established from Tyro3-knockout mouse dorsal root ganglia (DRG). Indeed, Tyro3-knockout mice exhibit reduced myelin thickness. By affinity chromatography, Fyn was identified as the binding partner of the Tyro3 intracellular domain, and activity of Fyn is down-regulated in Tyro3-knockout mice, suggesting that Tyro3, acting through Fyn, regulates myelination. Ablating Fyn in mice results in reduced myelin thickness. Decreased myelin formation is observed in cultures established from Fyn-knockout mouse DRG. Furthermore, decreased kinase activity levels and altered expression of myelination-associated transcription factors are observed in these knockout mice. These results suggest the involvement of Tyro3 receptor and its binding partner Fyn in Schwann cell myelination. This constitutes a newly recognized receptor-linked signaling mechanism that can control Schwann cell myelination. The American Society for Cell Biology 2015-10-01 /pmc/articles/PMC4591693/ /pubmed/26224309 http://dx.doi.org/10.1091/mbc.E14-05-1020 Text en © 2015 Miyamoto et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. |
spellingShingle | Articles Miyamoto, Yuki Torii, Tomohiro Takada, Shuji Ohno, Nobuhiko Saitoh, Yurika Nakamura, Kazuaki Ito, Akihito Ogata, Toru Terada, Nobuo Tanoue, Akito Yamauchi, Junji Involvement of the Tyro3 receptor and its intracellular partner Fyn signaling in Schwann cell myelination |
title | Involvement of the Tyro3 receptor and its intracellular partner Fyn signaling in Schwann cell myelination |
title_full | Involvement of the Tyro3 receptor and its intracellular partner Fyn signaling in Schwann cell myelination |
title_fullStr | Involvement of the Tyro3 receptor and its intracellular partner Fyn signaling in Schwann cell myelination |
title_full_unstemmed | Involvement of the Tyro3 receptor and its intracellular partner Fyn signaling in Schwann cell myelination |
title_short | Involvement of the Tyro3 receptor and its intracellular partner Fyn signaling in Schwann cell myelination |
title_sort | involvement of the tyro3 receptor and its intracellular partner fyn signaling in schwann cell myelination |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4591693/ https://www.ncbi.nlm.nih.gov/pubmed/26224309 http://dx.doi.org/10.1091/mbc.E14-05-1020 |
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