PUBLICATION

Stac3 is a component of the excitation-contraction coupling machinery and mutated in Native American myopathy

Authors
Horstick, E.J., Linsley, J.W., Dowling, J.J., Hauser, M.A., McDonald, K.K., Ashley-Koch, A., Saint-Amant, L., Satish, A., Cui, W.W., Zhou, W., Sprague, S.M., Stamm, D.S., Powell, C.M., Speer, M.C., Franzini-Armstrong, C., Hirata, H., and Kuwada, J.Y.
ID
ZDB-PUB-130709-4
Date
2013
Source
Nature communications   4: 1952 (Journal)
Registered Authors
Cui, Wilson, Dowling, Jim, Hirata, Hiromi, Kuwada, John, Saint-Amant, Louis, Sprague, Shawn, Zhou, Weibin
Keywords
none
MeSH Terms
  • Adaptor Proteins, Signal Transducing/chemistry
  • Adaptor Proteins, Signal Transducing/genetics*
  • Adaptor Proteins, Signal Transducing/metabolism
  • Alleles
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Central Nervous System/metabolism
  • Central Nervous System/pathology
  • Cleft Palate/genetics*
  • Cleft Palate/physiopathology*
  • Embryo, Nonmammalian/metabolism
  • Excitation Contraction Coupling*
  • Humans
  • Malignant Hyperthermia/genetics*
  • Malignant Hyperthermia/physiopathology*
  • Molecular Sequence Data
  • Mutation/genetics*
  • Mutation, Missense/genetics
  • Myofibrils/metabolism
  • Myofibrils/ultrastructure
  • Myotonia Congenita/genetics*
  • Myotonia Congenita/pathology
  • Myotonia Congenita/physiopathology*
  • Nerve Tissue Proteins/chemistry
  • Nerve Tissue Proteins/genetics*
  • Nerve Tissue Proteins/metabolism
  • Organ Specificity/genetics
  • Phenotype
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • Ryanodine Receptor Calcium Release Channel/metabolism
  • Swimming
  • Touch
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish Proteins/chemistry
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
PubMed
23736855 Full text @ Nat. Commun.
Abstract
Excitation–contraction coupling, the process that regulates contractions by skeletal muscles, transduces changes in membrane voltage by activating release of Ca2+ from internal stores to initiate muscle contraction. Defects in excitation–contraction coupling are associated with muscle diseases. Here we identify Stac3 as a novel component of the excitation–contraction coupling machinery. Using a zebrafish genetic screen, we generate a locomotor mutation that is mapped to stac3. We provide electrophysiological, Ca2+ imaging, immunocytochemical and biochemical evidence that Stac3 participates in excitation–contraction coupling in muscles. Furthermore, we reveal that a mutation in human STAC3 is the genetic basis of the debilitating Native American myopathy (NAM). Analysis of NAM stac3 in zebrafish shows that the NAM mutation decreases excitation–contraction coupling. These findings enhance our understanding of both excitation–contraction coupling and the pathology of myopathies.
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