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Tropomodulin isoforms regulate thin filament pointed-end capping and skeletal muscle physiology

During myofibril assembly, thin filament lengths are precisely specified to optimize skeletal muscle function. Tropomodulins (Tmods) are capping proteins that specify thin filament lengths by controlling actin dynamics at pointed ends. In this study, we use a genetic targeting approach to explore th...

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Autores principales: Gokhin, David S., Lewis, Raymond A., McKeown, Caroline R., Nowak, Roberta B., Kim, Nancy E., Littlefield, Ryan S., Lieber, Richard L., Fowler, Velia M.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2854367/
https://www.ncbi.nlm.nih.gov/pubmed/20368620
http://dx.doi.org/10.1083/jcb.201001125
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author Gokhin, David S.
Lewis, Raymond A.
McKeown, Caroline R.
Nowak, Roberta B.
Kim, Nancy E.
Littlefield, Ryan S.
Lieber, Richard L.
Fowler, Velia M.
author_facet Gokhin, David S.
Lewis, Raymond A.
McKeown, Caroline R.
Nowak, Roberta B.
Kim, Nancy E.
Littlefield, Ryan S.
Lieber, Richard L.
Fowler, Velia M.
author_sort Gokhin, David S.
collection PubMed
description During myofibril assembly, thin filament lengths are precisely specified to optimize skeletal muscle function. Tropomodulins (Tmods) are capping proteins that specify thin filament lengths by controlling actin dynamics at pointed ends. In this study, we use a genetic targeting approach to explore the effects of deleting Tmod1 from skeletal muscle. Myofibril assembly, skeletal muscle structure, and thin filament lengths are normal in the absence of Tmod1. Tmod4 localizes to thin filament pointed ends in Tmod1-null embryonic muscle, whereas both Tmod3 and -4 localize to pointed ends in Tmod1-null adult muscle. Substitution by Tmod3 and -4 occurs despite their weaker interactions with striated muscle tropomyosins. However, the absence of Tmod1 results in depressed isometric stress production during muscle contraction, systemic locomotor deficits, and a shift to a faster fiber type distribution. Thus, Tmod3 and -4 compensate for the absence of Tmod1 structurally but not functionally. We conclude that Tmod1 is a novel regulator of skeletal muscle physiology.
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spelling pubmed-28543672010-10-05 Tropomodulin isoforms regulate thin filament pointed-end capping and skeletal muscle physiology Gokhin, David S. Lewis, Raymond A. McKeown, Caroline R. Nowak, Roberta B. Kim, Nancy E. Littlefield, Ryan S. Lieber, Richard L. Fowler, Velia M. J Cell Biol Research Articles During myofibril assembly, thin filament lengths are precisely specified to optimize skeletal muscle function. Tropomodulins (Tmods) are capping proteins that specify thin filament lengths by controlling actin dynamics at pointed ends. In this study, we use a genetic targeting approach to explore the effects of deleting Tmod1 from skeletal muscle. Myofibril assembly, skeletal muscle structure, and thin filament lengths are normal in the absence of Tmod1. Tmod4 localizes to thin filament pointed ends in Tmod1-null embryonic muscle, whereas both Tmod3 and -4 localize to pointed ends in Tmod1-null adult muscle. Substitution by Tmod3 and -4 occurs despite their weaker interactions with striated muscle tropomyosins. However, the absence of Tmod1 results in depressed isometric stress production during muscle contraction, systemic locomotor deficits, and a shift to a faster fiber type distribution. Thus, Tmod3 and -4 compensate for the absence of Tmod1 structurally but not functionally. We conclude that Tmod1 is a novel regulator of skeletal muscle physiology. The Rockefeller University Press 2010-04-05 /pmc/articles/PMC2854367/ /pubmed/20368620 http://dx.doi.org/10.1083/jcb.201001125 Text en © 2010 Gokhin 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
Gokhin, David S.
Lewis, Raymond A.
McKeown, Caroline R.
Nowak, Roberta B.
Kim, Nancy E.
Littlefield, Ryan S.
Lieber, Richard L.
Fowler, Velia M.
Tropomodulin isoforms regulate thin filament pointed-end capping and skeletal muscle physiology
title Tropomodulin isoforms regulate thin filament pointed-end capping and skeletal muscle physiology
title_full Tropomodulin isoforms regulate thin filament pointed-end capping and skeletal muscle physiology
title_fullStr Tropomodulin isoforms regulate thin filament pointed-end capping and skeletal muscle physiology
title_full_unstemmed Tropomodulin isoforms regulate thin filament pointed-end capping and skeletal muscle physiology
title_short Tropomodulin isoforms regulate thin filament pointed-end capping and skeletal muscle physiology
title_sort tropomodulin isoforms regulate thin filament pointed-end capping and skeletal muscle physiology
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2854367/
https://www.ncbi.nlm.nih.gov/pubmed/20368620
http://dx.doi.org/10.1083/jcb.201001125
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