Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Gohlke, Jochen, Tonino, Paola, Lindqvist, Johan, Smith, John E., Granzier, Henk
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2020
Materias:
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
_version_ 1783626240793509888
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
work_keys_str_mv AT gohlkejochen thenumberofzrepeatsandsuperrepeatsinnebulingreatlyvariesacrossvertebratesandscaleswithanimalsize
AT toninopaola thenumberofzrepeatsandsuperrepeatsinnebulingreatlyvariesacrossvertebratesandscaleswithanimalsize
AT lindqvistjohan thenumberofzrepeatsandsuperrepeatsinnebulingreatlyvariesacrossvertebratesandscaleswithanimalsize
AT smithjohne thenumberofzrepeatsandsuperrepeatsinnebulingreatlyvariesacrossvertebratesandscaleswithanimalsize
AT granzierhenk thenumberofzrepeatsandsuperrepeatsinnebulingreatlyvariesacrossvertebratesandscaleswithanimalsize
AT gohlkejochen numberofzrepeatsandsuperrepeatsinnebulingreatlyvariesacrossvertebratesandscaleswithanimalsize
AT toninopaola numberofzrepeatsandsuperrepeatsinnebulingreatlyvariesacrossvertebratesandscaleswithanimalsize
AT lindqvistjohan numberofzrepeatsandsuperrepeatsinnebulingreatlyvariesacrossvertebratesandscaleswithanimalsize
AT smithjohne numberofzrepeatsandsuperrepeatsinnebulingreatlyvariesacrossvertebratesandscaleswithanimalsize
AT granzierhenk numberofzrepeatsandsuperrepeatsinnebulingreatlyvariesacrossvertebratesandscaleswithanimalsize