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The number of Z-repeats and super-repeats in nebulin greatly varies across vertebrates and scales with animal size
Nebulin is a skeletal muscle protein that associates with the sarcomeric thin filaments and has functions in regulating the length of the thin filament and the structure of the Z-disk. Here we investigated the nebulin gene in 53 species of birds, fish, amphibians, reptiles, and mammals. In all speci...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Rockefeller University Press
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754682/ https://www.ncbi.nlm.nih.gov/pubmed/33337482 http://dx.doi.org/10.1085/jgp.202012783 |
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author | Gohlke, Jochen Tonino, Paola Lindqvist, Johan Smith, John E. Granzier, Henk |
author_facet | Gohlke, Jochen Tonino, Paola Lindqvist, Johan Smith, John E. Granzier, Henk |
author_sort | Gohlke, Jochen |
collection | PubMed |
description | Nebulin is a skeletal muscle protein that associates with the sarcomeric thin filaments and has functions in regulating the length of the thin filament and the structure of the Z-disk. Here we investigated the nebulin gene in 53 species of birds, fish, amphibians, reptiles, and mammals. In all species, nebulin has a similar domain composition that mostly consists of ∼30-residue modules (or simple repeats), each containing an actin-binding site. All species have a large region where simple repeats are organized into seven-module super-repeats, each containing a tropomyosin binding site. The number of super-repeats shows high interspecies variation, ranging from 21 (zebrafish, hummingbird) to 31 (camel, chimpanzee), and, importantly, scales with body size. The higher number of super-repeats in large animals was shown to increase thin filament length, which is expected to increase the sarcomere length for optimal force production, increase the energy efficiency of isometric force production, and lower the shortening velocity of muscle. It has been known since the work of A.V. Hill in 1950 that as species increase in size, the shortening velocity of their muscle is reduced, and the present work shows that nebulin contributes to the mechanistic basis. Finally, we analyzed the differentially spliced simple repeats in nebulin's C terminus, whose inclusion correlates with the width of the Z-disk. The number of Z-repeats greatly varies (from 5 to 18) and correlates with the number of super-repeats. We propose that the resulting increase in the width of the Z-disk in large animals increases the number of contacts between nebulin and structural Z-disk proteins when the Z-disk is stressed for long durations. |
format | Online Article Text |
id | pubmed-7754682 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-77546822021-09-01 The number of Z-repeats and super-repeats in nebulin greatly varies across vertebrates and scales with animal size Gohlke, Jochen Tonino, Paola Lindqvist, Johan Smith, John E. Granzier, Henk J Gen Physiol Article Nebulin is a skeletal muscle protein that associates with the sarcomeric thin filaments and has functions in regulating the length of the thin filament and the structure of the Z-disk. Here we investigated the nebulin gene in 53 species of birds, fish, amphibians, reptiles, and mammals. In all species, nebulin has a similar domain composition that mostly consists of ∼30-residue modules (or simple repeats), each containing an actin-binding site. All species have a large region where simple repeats are organized into seven-module super-repeats, each containing a tropomyosin binding site. The number of super-repeats shows high interspecies variation, ranging from 21 (zebrafish, hummingbird) to 31 (camel, chimpanzee), and, importantly, scales with body size. The higher number of super-repeats in large animals was shown to increase thin filament length, which is expected to increase the sarcomere length for optimal force production, increase the energy efficiency of isometric force production, and lower the shortening velocity of muscle. It has been known since the work of A.V. Hill in 1950 that as species increase in size, the shortening velocity of their muscle is reduced, and the present work shows that nebulin contributes to the mechanistic basis. Finally, we analyzed the differentially spliced simple repeats in nebulin's C terminus, whose inclusion correlates with the width of the Z-disk. The number of Z-repeats greatly varies (from 5 to 18) and correlates with the number of super-repeats. We propose that the resulting increase in the width of the Z-disk in large animals increases the number of contacts between nebulin and structural Z-disk proteins when the Z-disk is stressed for long durations. Rockefeller University Press 2020-12-18 /pmc/articles/PMC7754682/ /pubmed/33337482 http://dx.doi.org/10.1085/jgp.202012783 Text en © 2020 Gohlke et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/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 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Article Gohlke, Jochen Tonino, Paola Lindqvist, Johan Smith, John E. Granzier, Henk The number of Z-repeats and super-repeats in nebulin greatly varies across vertebrates and scales with animal size |
title | The number of Z-repeats and super-repeats in nebulin greatly varies across vertebrates and scales with animal size |
title_full | The number of Z-repeats and super-repeats in nebulin greatly varies across vertebrates and scales with animal size |
title_fullStr | The number of Z-repeats and super-repeats in nebulin greatly varies across vertebrates and scales with animal size |
title_full_unstemmed | The number of Z-repeats and super-repeats in nebulin greatly varies across vertebrates and scales with animal size |
title_short | The number of Z-repeats and super-repeats in nebulin greatly varies across vertebrates and scales with animal size |
title_sort | number of z-repeats and super-repeats in nebulin greatly varies across vertebrates and scales with animal size |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754682/ https://www.ncbi.nlm.nih.gov/pubmed/33337482 http://dx.doi.org/10.1085/jgp.202012783 |
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