Interactions among ryanodine receptor isotypes contribute to muscle fiber type development and function
Mutations affecting ryanodine receptor (RyR) calcium release channels commonly underlie congenital myopathies. Although these channels are known principally for their essential roles in muscle contractility, mutations in the human RYR1 gene result in a broad spectrum of phenotypes, including muscle...
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The Company of Biologists
2020-02-01
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doaj-ad67ad78e2774fb69c0b67ec49188b7f2020-11-25T01:57:56ZengThe Company of BiologistsDisease Models & Mechanisms1754-84031754-84112020-02-0113210.1242/dmm.038844038844Interactions among ryanodine receptor isotypes contribute to muscle fiber type development and functionAlexis A. Chagovetz0Dana Klatt Shaw1Erin Ritchie2Kazuyuki Hoshijima3David J. Grunwald4Annemieke Aartsma-Rus5James Dowling6Maaike van Putten7 Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA Mutations affecting ryanodine receptor (RyR) calcium release channels commonly underlie congenital myopathies. Although these channels are known principally for their essential roles in muscle contractility, mutations in the human RYR1 gene result in a broad spectrum of phenotypes, including muscle weakness, altered proportions of fiber types, anomalous muscle fibers with cores or centrally placed nuclei, and dysmorphic craniofacial features. Currently, it is unknown which phenotypes directly reflect requirements for RyRs and which result secondarily to aberrant muscle function. To identify biological processes requiring RyR function, skeletal muscle development was analyzed in zebrafish embryos harboring protein-null mutations. RyR channels contribute to both muscle fiber development and function. Loss of some RyRs had modest effects, altering muscle fiber-type specification in the embryo without compromising viability. In addition, each RyR-encoding gene contributed to normal swimming behavior and muscle function. The RyR channels do not function in a simple additive manner. For example, although isoform RyR1a is sufficient for muscle contraction in the absence of RyR1b, RyR1a normally attenuates the activity of the co-expressed RyR1b channel in slow muscle. RyR3 also acts to modify the functions of other RyR channels. Furthermore, diminished RyR-dependent contractility affects both muscle fiber maturation and craniofacial development. These findings help to explain some of the heterogeneity of phenotypes that accompany RyR1 mutations in humans.http://dmm.biologists.org/content/13/2/dmm038844ryanodine receptorscongenital myopathyzebrafish disease modelmuscle developmentmuscle function |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Alexis A. Chagovetz Dana Klatt Shaw Erin Ritchie Kazuyuki Hoshijima David J. Grunwald Annemieke Aartsma-Rus James Dowling Maaike van Putten |
spellingShingle |
Alexis A. Chagovetz Dana Klatt Shaw Erin Ritchie Kazuyuki Hoshijima David J. Grunwald Annemieke Aartsma-Rus James Dowling Maaike van Putten Interactions among ryanodine receptor isotypes contribute to muscle fiber type development and function Disease Models & Mechanisms ryanodine receptors congenital myopathy zebrafish disease model muscle development muscle function |
author_facet |
Alexis A. Chagovetz Dana Klatt Shaw Erin Ritchie Kazuyuki Hoshijima David J. Grunwald Annemieke Aartsma-Rus James Dowling Maaike van Putten |
author_sort |
Alexis A. Chagovetz |
title |
Interactions among ryanodine receptor isotypes contribute to muscle fiber type development and function |
title_short |
Interactions among ryanodine receptor isotypes contribute to muscle fiber type development and function |
title_full |
Interactions among ryanodine receptor isotypes contribute to muscle fiber type development and function |
title_fullStr |
Interactions among ryanodine receptor isotypes contribute to muscle fiber type development and function |
title_full_unstemmed |
Interactions among ryanodine receptor isotypes contribute to muscle fiber type development and function |
title_sort |
interactions among ryanodine receptor isotypes contribute to muscle fiber type development and function |
publisher |
The Company of Biologists |
series |
Disease Models & Mechanisms |
issn |
1754-8403 1754-8411 |
publishDate |
2020-02-01 |
description |
Mutations affecting ryanodine receptor (RyR) calcium release channels commonly underlie congenital myopathies. Although these channels are known principally for their essential roles in muscle contractility, mutations in the human RYR1 gene result in a broad spectrum of phenotypes, including muscle weakness, altered proportions of fiber types, anomalous muscle fibers with cores or centrally placed nuclei, and dysmorphic craniofacial features. Currently, it is unknown which phenotypes directly reflect requirements for RyRs and which result secondarily to aberrant muscle function. To identify biological processes requiring RyR function, skeletal muscle development was analyzed in zebrafish embryos harboring protein-null mutations. RyR channels contribute to both muscle fiber development and function. Loss of some RyRs had modest effects, altering muscle fiber-type specification in the embryo without compromising viability. In addition, each RyR-encoding gene contributed to normal swimming behavior and muscle function. The RyR channels do not function in a simple additive manner. For example, although isoform RyR1a is sufficient for muscle contraction in the absence of RyR1b, RyR1a normally attenuates the activity of the co-expressed RyR1b channel in slow muscle. RyR3 also acts to modify the functions of other RyR channels. Furthermore, diminished RyR-dependent contractility affects both muscle fiber maturation and craniofacial development. These findings help to explain some of the heterogeneity of phenotypes that accompany RyR1 mutations in humans. |
topic |
ryanodine receptors congenital myopathy zebrafish disease model muscle development muscle function |
url |
http://dmm.biologists.org/content/13/2/dmm038844 |
work_keys_str_mv |
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