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Effects of Purified Recombinant Neural and Muscle Agrin on Skeletal Muscle Fibers in Vivo

Aggregation of acetylcholine receptors (AChRs) in muscle fibers by nerve-derived agrin plays a key role in the formation of neuromuscular junctions. So far, the effects of agrin on muscle fibers have been studied in culture systems, transgenic animals, and in animals injected with agrin–cDNA constru...

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Autores principales: Bezakova, Gabriela, Helm, Johannes P., Francolini, Maura, Lømo, Terje
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2001
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2150725/
https://www.ncbi.nlm.nih.gov/pubmed/11425874
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author Bezakova, Gabriela
Helm, Johannes P.
Francolini, Maura
Lømo, Terje
author_facet Bezakova, Gabriela
Helm, Johannes P.
Francolini, Maura
Lømo, Terje
author_sort Bezakova, Gabriela
collection PubMed
description Aggregation of acetylcholine receptors (AChRs) in muscle fibers by nerve-derived agrin plays a key role in the formation of neuromuscular junctions. So far, the effects of agrin on muscle fibers have been studied in culture systems, transgenic animals, and in animals injected with agrin–cDNA constructs. We have applied purified recombinant chick neural and muscle agrin to rat soleus muscle in vivo and obtained the following results. Both neural and muscle agrin bind uniformly to the surface of innervated and denervated muscle fibers along their entire length. Neural agrin causes a dose-dependent appearance of AChR aggregates, which persist ≥7 wk after a single application. Muscle agrin does not cluster AChRs and at 10 times the concentration of neural agrin does not reduce binding or AChR-aggregating activity of neural agrin. Electrical muscle activity affects the stability of agrin binding and the number, size, and spatial distribution of the neural agrin–induced AChR aggregates. Injected agrin is recovered from the muscles together with laminin and both proteins coimmunoprecipitate, indicating that agrin binds to laminin in vivo. Thus, the present approach provides a novel, simple, and efficient method for studying the effects of agrin on muscle under controlled conditions in vivo.
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spelling pubmed-21507252008-05-01 Effects of Purified Recombinant Neural and Muscle Agrin on Skeletal Muscle Fibers in Vivo Bezakova, Gabriela Helm, Johannes P. Francolini, Maura Lømo, Terje J Cell Biol Original Article Aggregation of acetylcholine receptors (AChRs) in muscle fibers by nerve-derived agrin plays a key role in the formation of neuromuscular junctions. So far, the effects of agrin on muscle fibers have been studied in culture systems, transgenic animals, and in animals injected with agrin–cDNA constructs. We have applied purified recombinant chick neural and muscle agrin to rat soleus muscle in vivo and obtained the following results. Both neural and muscle agrin bind uniformly to the surface of innervated and denervated muscle fibers along their entire length. Neural agrin causes a dose-dependent appearance of AChR aggregates, which persist ≥7 wk after a single application. Muscle agrin does not cluster AChRs and at 10 times the concentration of neural agrin does not reduce binding or AChR-aggregating activity of neural agrin. Electrical muscle activity affects the stability of agrin binding and the number, size, and spatial distribution of the neural agrin–induced AChR aggregates. Injected agrin is recovered from the muscles together with laminin and both proteins coimmunoprecipitate, indicating that agrin binds to laminin in vivo. Thus, the present approach provides a novel, simple, and efficient method for studying the effects of agrin on muscle under controlled conditions in vivo. The Rockefeller University Press 2001-06-25 /pmc/articles/PMC2150725/ /pubmed/11425874 Text en © 2001 The Rockefeller University Press 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 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Original Article
Bezakova, Gabriela
Helm, Johannes P.
Francolini, Maura
Lømo, Terje
Effects of Purified Recombinant Neural and Muscle Agrin on Skeletal Muscle Fibers in Vivo
title Effects of Purified Recombinant Neural and Muscle Agrin on Skeletal Muscle Fibers in Vivo
title_full Effects of Purified Recombinant Neural and Muscle Agrin on Skeletal Muscle Fibers in Vivo
title_fullStr Effects of Purified Recombinant Neural and Muscle Agrin on Skeletal Muscle Fibers in Vivo
title_full_unstemmed Effects of Purified Recombinant Neural and Muscle Agrin on Skeletal Muscle Fibers in Vivo
title_short Effects of Purified Recombinant Neural and Muscle Agrin on Skeletal Muscle Fibers in Vivo
title_sort effects of purified recombinant neural and muscle agrin on skeletal muscle fibers in vivo
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2150725/
https://www.ncbi.nlm.nih.gov/pubmed/11425874
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