Interactions among Ryanodine Receptor isotypes contribute to muscle fiber type development and function
| Autor: | Alexis A. Chagovetz, Dana Klatt Shaw, Erin Ritchie, Kazuyuki Hoshijima, David J. Grunwald, Annemieke Aartsma-Rus, James Dowling, Maaike van Putten |
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| Rok vydání: | 2019 |
| Předmět: |
Ryanodine receptors
0301 basic medicine Reflex Startle Embryo Nonmammalian Muscle Fibers Skeletal lcsh:Medicine Medicine (miscellaneous) Zebrafish disease model 0302 clinical medicine Immunology and Microbiology (miscellaneous) Morphogenesis Muscle development Zebrafish Congenital myopathy Behavior Animal Ryanodine receptor musculoskeletal system Cell biology medicine.anatomical_structure cardiovascular system medicine.symptom tissues lcsh:RB1-214 Muscle Contraction Protein Binding Research Article Muscle contraction Gene isoform Neuroscience (miscellaneous) Biology General Biochemistry Genetics and Molecular Biology Contractility 03 medical and health sciences lcsh:Pathology medicine Animals Calcium Signaling Alleles Swimming RYR1 lcsh:R Skull Skeletal muscle Muscle weakness Ryanodine Receptor Calcium Release Channel Zebrafish Proteins medicine.disease 030104 developmental biology Muscle function Face Mutation 030217 neurology & neurosurgery |
| Zdroj: | Disease Models & Mechanisms Disease Models & Mechanisms, Vol 13, Iss 2 (2020) |
| ISSN: | 1754-8411 1754-8403 |
| DOI: | 10.1242/dmm.038844 |
| Popis: | 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. Summary: Skeletal muscle fiber development and function are dependent on additive as well as combinatorial interactions among ryanodine receptor calcium release channels. |
| Databáze: | OpenAIRE |
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