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Agrin regulates CLASP2-mediated capture of microtubules at the neuromuscular junction synaptic membrane
Agrin is the major factor mediating the neuronal regulation of postsynaptic structures at the vertebrate neuromuscular junction, but the details of how it orchestrates this unique three-dimensional structure remain unknown. Here, we show that agrin induces the formation of the dense network of micro...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3413356/ https://www.ncbi.nlm.nih.gov/pubmed/22851317 http://dx.doi.org/10.1083/jcb.201111130 |
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author | Schmidt, Nadine Basu, Sreya Sladecek, Stefan Gatti, Sabrina van Haren, Jeffrey Treves, Susan Pielage, Jan Galjart, Niels Brenner, Hans Rudolf |
author_facet | Schmidt, Nadine Basu, Sreya Sladecek, Stefan Gatti, Sabrina van Haren, Jeffrey Treves, Susan Pielage, Jan Galjart, Niels Brenner, Hans Rudolf |
author_sort | Schmidt, Nadine |
collection | PubMed |
description | Agrin is the major factor mediating the neuronal regulation of postsynaptic structures at the vertebrate neuromuscular junction, but the details of how it orchestrates this unique three-dimensional structure remain unknown. Here, we show that agrin induces the formation of the dense network of microtubules in the subsynaptic cytoplasm and that this, in turn, regulates acetylcholine receptor insertion into the postsynaptic membrane. Agrin acted in part by locally activating phosphatidylinositol 3-kinase and inactivating GSK3β, which led to the local capturing of dynamic microtubules at agrin-induced acetylcholine receptor (AChR) clusters, mediated to a large extent by the microtubule plus-end tracking proteins CLASP2 and CLIP-170. Indeed, in the absence of CLASP2, microtubule plus ends at the subsynaptic muscle membrane, the density of synaptic AChRs, the size of AChR clusters, and the numbers of subsynaptic muscle nuclei with their selective gene expression programs were all reduced. Thus, the cascade linking agrin to CLASP2-mediated microtubule capturing at the synaptic membrane is essential for the maintenance of a normal neuromuscular phenotype. |
format | Online Article Text |
id | pubmed-3413356 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-34133562013-02-06 Agrin regulates CLASP2-mediated capture of microtubules at the neuromuscular junction synaptic membrane Schmidt, Nadine Basu, Sreya Sladecek, Stefan Gatti, Sabrina van Haren, Jeffrey Treves, Susan Pielage, Jan Galjart, Niels Brenner, Hans Rudolf J Cell Biol Research Articles Agrin is the major factor mediating the neuronal regulation of postsynaptic structures at the vertebrate neuromuscular junction, but the details of how it orchestrates this unique three-dimensional structure remain unknown. Here, we show that agrin induces the formation of the dense network of microtubules in the subsynaptic cytoplasm and that this, in turn, regulates acetylcholine receptor insertion into the postsynaptic membrane. Agrin acted in part by locally activating phosphatidylinositol 3-kinase and inactivating GSK3β, which led to the local capturing of dynamic microtubules at agrin-induced acetylcholine receptor (AChR) clusters, mediated to a large extent by the microtubule plus-end tracking proteins CLASP2 and CLIP-170. Indeed, in the absence of CLASP2, microtubule plus ends at the subsynaptic muscle membrane, the density of synaptic AChRs, the size of AChR clusters, and the numbers of subsynaptic muscle nuclei with their selective gene expression programs were all reduced. Thus, the cascade linking agrin to CLASP2-mediated microtubule capturing at the synaptic membrane is essential for the maintenance of a normal neuromuscular phenotype. The Rockefeller University Press 2012-08-06 /pmc/articles/PMC3413356/ /pubmed/22851317 http://dx.doi.org/10.1083/jcb.201111130 Text en © 2012 Schmidt 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.rupress.org/terms). 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 Schmidt, Nadine Basu, Sreya Sladecek, Stefan Gatti, Sabrina van Haren, Jeffrey Treves, Susan Pielage, Jan Galjart, Niels Brenner, Hans Rudolf Agrin regulates CLASP2-mediated capture of microtubules at the neuromuscular junction synaptic membrane |
title | Agrin regulates CLASP2-mediated capture of microtubules at the neuromuscular junction synaptic membrane |
title_full | Agrin regulates CLASP2-mediated capture of microtubules at the neuromuscular junction synaptic membrane |
title_fullStr | Agrin regulates CLASP2-mediated capture of microtubules at the neuromuscular junction synaptic membrane |
title_full_unstemmed | Agrin regulates CLASP2-mediated capture of microtubules at the neuromuscular junction synaptic membrane |
title_short | Agrin regulates CLASP2-mediated capture of microtubules at the neuromuscular junction synaptic membrane |
title_sort | agrin regulates clasp2-mediated capture of microtubules at the neuromuscular junction synaptic membrane |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3413356/ https://www.ncbi.nlm.nih.gov/pubmed/22851317 http://dx.doi.org/10.1083/jcb.201111130 |
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