PUBLICATION

Interactions among Ryanodine Receptor isotypes contribute to muscle fiber type development and function

Authors
Chagovetz, A.A., Klatt Shaw, D., Ritchie, E., Hoshijima, K., Grunwald, D.J.
ID
ZDB-PUB-190807-14
Date
2019
Source
Disease models & mechanisms   13(2): (Journal)
Registered Authors
Grunwald, David, Hoshijima, Kazuyuki
Keywords
Congenital myopathy, Muscle development, Muscle function, Ryanodine receptors, Zebrafish disease model
MeSH Terms
  • Alleles
  • Animals
  • Behavior, Animal
  • Calcium Signaling
  • Embryo, Nonmammalian/metabolism
  • Face/embryology
  • Morphogenesis
  • Muscle Contraction
  • Muscle Fibers, Skeletal/metabolism*
  • Mutation/genetics
  • Protein Binding
  • Reflex, Startle
  • Ryanodine Receptor Calcium Release Channel/metabolism*
  • Skull/embryology
  • Swimming
  • Zebrafish/embryology
  • Zebrafish/metabolism*
  • Zebrafish Proteins/metabolism
PubMed
31383689 Full text @ Dis. Model. Mech.
Abstract
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 ryr 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 gene contributed to normal swimming behavior and muscle function. The RyR channels do not function in a simple additive manner. For example, although 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. Finally, 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.
Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes