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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...

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Autores principales: Koppel, Natasha, Friese, Matthew B., Cardasis, Helene L., Neubert, Thomas A., Burden, Steven J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2019
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.
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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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