ArticleProceedings of the National Academy of Sciences of the United States of America2016
Stac3 has a direct role in skeletal muscle-type excitation-contraction coupling that is disrupted by a myopathy-causing mutation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 74 citations in OpenAlex.
- LL-37 Inhibits EV71 Infection by Upregulating STAC via the EGFR-ERK Signaling Pathway.Viruses · 2026Article
- Article
- STAC3 binding to CaV1.1 II-III loop is nonessential but critically supports skeletal muscle excitation-contraction coupling.JCI insight · 2025Article
- Two zebrafish cacna1s loss-of-function variants provide models of mild and severe CACNA1S-related myopathy.Human molecular genetics · 2024Article
- Advances in CaChannels (Austin, Tex.) · 2023Review
- Speg interactions that regulate the stability of excitation-contraction coupling protein complexes in triads and dyads.Communications biology · 2023Article
- A Systematic Compilation of Human SH3 Domains: A Versatile Superfamily in Cellular Signaling.Cells · 2023Review
- CaHandbook of experimental pharmacology · 2023Article
- NMJ-related diseases beyond the congenital myasthenic syndromes.Frontiers in cell and developmental biology · 2023Review
- A reconstituted depolarization-induced Ca2+ release platform for validation of skeletal muscle disease mutations and drug discovery.The Journal of general physiology · 2022Article
- Calcium current modulation by the γ1 subunit depends on alternative splicing of CaV1.1.The Journal of general physiology · 2022Article
- Mutations in proteins involved in E-C coupling and SOCE and congenital myopathies.The Journal of general physiology · 2022Review
- Morphological and Molecular Responses ofInternational journal of molecular sciences · 2022Article
- Molecular interactions of STAC proteins with skeletal muscle dihydropyridine receptor and excitation-contraction coupling.Protein science : a publication of the Protein Society · 2022Article
- The Sarcoplasmic Reticulum of Skeletal Muscle Cells: A Labyrinth of Membrane Contact Sites.Biomolecules · 2022Review
- Structures of the junctophilin/voltage-gated calcium channel interface reveal hot spot for cardiomyopathy mutations.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- The Builders of the Junction: Roles of Junctophilin1 and Junctophilin2 in the Assembly of the Sarcoplasmic Reticulum-Plasma Membrane Junctions in Striated Muscle.Biomolecules · 2022Review
- Clinical Features of Suspected Malignant Hyperthermia in China from 2015 to 2020: A Retrospective Study from China Malignant Hyperthermia Emergency Assistance Group.Journal of multidisciplinary healthcare · 2022Article
- Pannexin-1 and CaV1.1 show reciprocal interaction during excitation-contraction and excitation-transcription coupling in skeletal muscle.The Journal of general physiology · 2021Article
- Molecular and cellular basis of genetically inherited skeletal muscle disorders.Nature reviews. Molecular cell biology · 2021Review
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
In skeletal muscle, conformational coupling between CaV1.1 in the plasma membrane and type 1 ryanodine receptor (RyR1) in the sarcoplasmic reticulum (SR) is thought to underlie both excitation-contraction (EC) coupling Ca(2+) release from the SR and retrograde coupling by which RyR1 increases the magnitude of the Ca(2+) current via CaV1.1. Recent work has shown that EC coupling fails in muscle from mice and fish null for the protein Stac3 (SH3 and cysteine-rich domain 3) but did not establish the functional role of Stac3 in the CaV1.1-RyR1 interaction. We investigated this using both tsA201 cells and Stac3 KO myotubes. While confirming in tsA201 cells that Stac3 could support surface expression of CaV1.1 (coexpressed with its auxiliary β1a and α2-δ1 subunits) and the generation of large Ca(2+) currents, we found that without Stac3 the auxiliary γ1 subunit also supported membrane expression of CaV1.1/β1a/α2-δ1, but that this combination generated only tiny Ca(2+) currents. In Stac3 KO myotubes, there was reduced, but still substantial CaV1.1 in the plasma membrane. However, the CaV1.1 remaining in Stac3 KO myotubes did not generate appreciable Ca(2+) currents or EC coupling Ca(2+) release. Expression of WT Stac3 in Stac3 KO myotubes fully restored Ca(2+) currents and EC coupling Ca(2+) release, whereas expression of Stac3W280S (containing the Native American myopathy mutation) partially restored Ca(2+) currents but only marginally restored EC coupling. We conclude that membrane trafficking of CaV1.1 is facilitated by, but does not require, Stac3, and that Stac3 is directly involved in conformational coupling between CaV1.1 and RyR1.
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