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Vezatin is required for the maturation of the neuromuscular synapse
Key genes, such as Agrin, Lrp4, and MuSK, are required for the initial formation, subsequent maturation, and long-term stabilization of mammalian neuromuscular synapses. Additional molecules are thought to function selectively during the evolution and stabilization of these synapses, but these molec...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6740198/ https://www.ncbi.nlm.nih.gov/pubmed/31411944 http://dx.doi.org/10.1091/mbc.E19-06-0313 |
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author | Koppel, Natasha Friese, Matthew B. Cardasis, Helene L. Neubert, Thomas A. Burden, Steven J. |
author_facet | Koppel, Natasha Friese, Matthew B. Cardasis, Helene L. Neubert, Thomas A. Burden, Steven J. |
author_sort | Koppel, Natasha |
collection | PubMed |
description | Key genes, such as Agrin, Lrp4, and MuSK, are required for the initial formation, subsequent maturation, and long-term stabilization of mammalian neuromuscular synapses. Additional molecules are thought to function selectively during the evolution and stabilization of these synapses, but these molecular players are largely unknown. Here, we used mass spectrometry to identify vezatin, a two-pass transmembrane protein, as an acetylcholine receptor (AChR)–associated protein, and we provide evidence that vezatin binds directly to AChRs. We show that vezatin is dispensable for the formation of synapses but plays a later role in the emergence of a topologically complex and branched shape of the synapse, as well as the stabilization of AChRs. In addition, neuromuscular synapses in vezatin mutant mice display premature signs of deterioration, normally found only during aging. Thus, vezatin has a selective role in the structural elaboration and postnatal maturation of murine neuromuscular synapses. |
format | Online Article Text |
id | pubmed-6740198 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-67401982019-11-30 Vezatin is required for the maturation of the neuromuscular synapse Koppel, Natasha Friese, Matthew B. Cardasis, Helene L. Neubert, Thomas A. Burden, Steven J. Mol Biol Cell Articles Key genes, such as Agrin, Lrp4, and MuSK, are required for the initial formation, subsequent maturation, and long-term stabilization of mammalian neuromuscular synapses. Additional molecules are thought to function selectively during the evolution and stabilization of these synapses, but these molecular players are largely unknown. Here, we used mass spectrometry to identify vezatin, a two-pass transmembrane protein, as an acetylcholine receptor (AChR)–associated protein, and we provide evidence that vezatin binds directly to AChRs. We show that vezatin is dispensable for the formation of synapses but plays a later role in the emergence of a topologically complex and branched shape of the synapse, as well as the stabilization of AChRs. In addition, neuromuscular synapses in vezatin mutant mice display premature signs of deterioration, normally found only during aging. Thus, vezatin has a selective role in the structural elaboration and postnatal maturation of murine neuromuscular synapses. The American Society for Cell Biology 2019-09-15 /pmc/articles/PMC6740198/ /pubmed/31411944 http://dx.doi.org/10.1091/mbc.E19-06-0313 Text en © 2019 Koppel et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. http://creativecommons.org/licenses/by-nc-sa/3.0 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. |
spellingShingle | Articles Koppel, Natasha Friese, Matthew B. Cardasis, Helene L. Neubert, Thomas A. Burden, Steven J. Vezatin is required for the maturation of the neuromuscular synapse |
title | Vezatin is required for the maturation of the neuromuscular synapse |
title_full | Vezatin is required for the maturation of the neuromuscular synapse |
title_fullStr | Vezatin is required for the maturation of the neuromuscular synapse |
title_full_unstemmed | Vezatin is required for the maturation of the neuromuscular synapse |
title_short | Vezatin is required for the maturation of the neuromuscular synapse |
title_sort | vezatin is required for the maturation of the neuromuscular synapse |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6740198/ https://www.ncbi.nlm.nih.gov/pubmed/31411944 http://dx.doi.org/10.1091/mbc.E19-06-0313 |
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