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
-
- Alleles
- Mutation/genetics*
- Amino Acid Sequence
- Myotonia Congenita/genetics*
- Myotonia Congenita/pathology
- Myotonia Congenita/physiopathology*
- Excitation Contraction Coupling*
- Swimming
- Zebrafish/embryology
- Zebrafish/genetics
- Nerve Tissue Proteins/chemistry
- Nerve Tissue Proteins/genetics*
- Nerve Tissue Proteins/metabolism
- Ryanodine Receptor Calcium Release Channel/metabolism
- Malignant Hyperthermia/genetics*
- Malignant Hyperthermia/physiopathology*
- Touch
- Organ Specificity/genetics
- RNA, Messenger/genetics
- RNA, Messenger/metabolism
- Central Nervous System/metabolism
- Central Nervous System/pathology
- Humans
- Embryo, Nonmammalian/metabolism
- Molecular Sequence Data
- Phenotype
- Myofibrils/metabolism
- Myofibrils/ultrastructure
- Mutation, Missense/genetics
- Zebrafish Proteins/chemistry
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- Animals
- Cleft Palate/genetics*
- Cleft Palate/physiopathology*
- Base Sequence
- Adaptor Proteins, Signal Transducing/chemistry
- Adaptor Proteins, Signal Transducing/genetics*
- Adaptor Proteins, Signal Transducing/metabolism
- PubMed
- 23736855 Full text @ Nat. Commun.
Citation
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. (2013) Stac3 is a component of the excitation-contraction coupling machinery and mutated in Native American myopathy. Nature communications. 4:1952.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping