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.
Skip Nav Destination
Close
Article navigation
1 March 2021
Article|
December 18 2020
The number of Z-repeats and super-repeats in nebulin greatly varies across vertebrates and scales with animal size
Jochen Gohlke
,
Jochen Gohlke
Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ
Search for other works by this author on:
Paola Tonino
,
Paola Tonino
Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ
Search for other works by this author on:
Johan Lindqvist
,
Johan Lindqvist
Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ
Search for other works by this author on:
John E. Smith, III
,
John E. Smith, III
Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ
Search for other works by this author on:
Henk Granzier
Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ
Correspondence to Henk Granzier: granzier@arizona.edu
Search for other works by this author on:
Jochen Gohlke
Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ
Paola Tonino
Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ
Johan Lindqvist
Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ
John E. Smith, III
Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ
Henk Granzier
Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ
Correspondence to Henk Granzier: granzier@arizona.edu
This work is part of a special collection on myofilament function and disease.
Received:
September 30 2020
Accepted:
November 20 2020
Online Issn: 1540-7748
Print Issn: 0022-1295
© 2020 Gohlke et al.
2020
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/).
J Gen Physiol (2021) 153 (3): e202012783.
Article history
Received:
September 30 2020
Accepted:
November 20 2020
Connected Content
Citation
Jochen Gohlke, Paola Tonino, Johan Lindqvist, John E. Smith, Henk Granzier; The number of Z-repeats and super-repeats in nebulin greatly varies across vertebrates and scales with animal size. J Gen Physiol 1 March 2021; 153 (3): e202012783. doi: https://doi.org/10.1085/jgp.202012783
Download citation file:
Close
Sign in
Don't already have an account? Register
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Sign in via your Institution
Sign in via your Institution
141
Views
0
Citations
Suggested Content
Nebulin and titin modulate cross-bridge cycling and length-dependent calcium sensitivity
J Gen Physiol (April,2019)
Nebulin no longer nebulous
J Gen Physiol (October,2018)
CHROMATOGRAPHY OF BLOOD-CLOTTING FACTORS AND SERUM PROTEINS ON COLUMNS OF DIATOMACEOUS EARTH
J Gen Physiol (July,1955)
Advertisement