ArticleThe Journal of biological chemistry2010
Skeletal muscle-specific calpain is an intracellular Na+-dependent protease.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 55 citations in OpenAlex.
- Oligomer-dependent and oligomer-independent pathogenesis of muscular dystrophy-associated mutations within the penta-EF-hand domain of calpain-3.The Journal of biological chemistry · 2026Article
- Case report: A novel mutation of the CAPN3 gene in a Chinese family with limb-girdle muscular dystrophy type 2A.Frontiers in genetics · 2024Article
- A retrospective study on the clinical and molecular outcomes of calpainopathy in a Turkish patient cohort.Turkish journal of medical sciences · 2024Article
- Calpain-3 Is Not a Sodium Dependent Protease and Simply Requires Calcium for Activation.International journal of molecular sciences · 2023Article
- Current and Future Therapeutic Strategies for Limb Girdle Muscular Dystrophy Type R1: Clinical and Experimental Approaches.Pathophysiology : the official journal of the International Society for Pathophysiology · 2021Review
- Developing fluorescence sensor probe to capture activated muscle-specific calpain-3 (CAPN3) in living muscle cells.Biology open · 2020Article
- Sodium Fluctuations in Astroglia and Their Potential Impact on Astrocyte Function.Frontiers in physiology · 2020Review
- Calcium Mechanisms in Limb-Girdle Muscular Dystrophy withInternational journal of molecular sciences · 2019Review
- Overview of the Muscle Cytoskeleton.Comprehensive Physiology · 2017Review
- Integrative variants, haplotypes and diplotypes of the CAPN3 and FRMD5 genes and several environmental exposures associate with serum lipid variables.Scientific reports · 2017Article
- Calpain research for drug discovery: challenges and potential.Nature reviews. Drug discovery · 2016Review
- Skeletal muscle as an endocrine organ: Role of [NaGenes & diseases · 2015Article
- Calpain-10 Activity Underlies Angiotensin II-Induced Aldosterone Production in an Adrenal Glomerulosa Cell Model.Endocrinology · 2015Article
- Salt and gene expression: evidence for [Na+]i/[K+]i-mediated signaling pathways.Pflugers Archiv : European journal of physiology · 2015Review
- The N- and C-terminal autolytic fragments of CAPN3/p94/calpain-3 restore proteolytic activity by intermolecular complementation.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Redox state and mitochondrial respiratory chain function in skeletal muscle of LGMD2A patients.PloS one · 2014Article
- PLEIAD/SIMC1/C5orf25, a novel autolysis regulator for a skeletal-muscle-specific calpain, CAPN3, scaffolds a CAPN3 substrate, CTBP1.Journal of molecular biology · 2013Article
- A New Insight into the Role of Calpains in Post-mortem Meat Tenderization in Domestic Animals: A review.Asian-Australasian journal of animal sciences · 2013Review
- Regulation and physiological roles of the calpain system in muscular disorders.Cardiovascular research · 2012Review
- Non-proteolytic functions of calpain-3 in sarcoplasmic reticulum in skeletal muscles.Journal of molecular biology · 2011Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Because intracellular [Na(+)] is kept low by Na(+)/K(+)-ATPase, Na(+) dependence is generally considered a property of extracellular enzymes. However, we found that p94/calpain 3, a skeletal-muscle-specific member of the Ca(2+)-activated intracellular "modulator proteases" that is responsible for a limb-girdle muscular dystrophy ("calpainopathy"), underwent Na(+)-dependent, but not Cs(+)-dependent, autolysis in the absence of Ca(2+). Furthermore, Na(+) and Ca(2+) complementarily activated autolysis of p94 at physiological concentrations. By blocking Na(+)/K(+)-ATPase, we confirmed intracellular autolysis of p94 in cultured cells. This was further confirmed using inactive p94:C129S knock-in (p94CS-KI) mice as negative controls. Mutagenesis studies showed that much of the p94 molecule contributed to its Na(+)/Ca(2+)-dependent autolysis, which is consistent with the scattered location of calpainopathy-associated mutations, and that a conserved Ca(2+)-binding sequence in the protease acted as a Na(+) sensor. Proteomic analyses using Cs(+)/Mg(2+) and p94CS-KI mice as negative controls revealed that Na(+) and Ca(2+) direct p94 to proteolyze different substrates. We propose three roles for Na(+) dependence of p94; 1) to increase sensitivity of p94 to changes in physiological [Ca(2+)], 2) to regulate substrate specificity of p94, and 3) to regulate contribution of p94 as a structural component in muscle cells. Finally, this is the first example of an intracellular Na(+)-dependent enzyme.
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