biostudies-literatureVillani KRNational Institute of Arthritis and Musculoskeletal and Skin DiseasesCoalition to Cure Calpain 3 FoundationNIAMS NIH HHSe23825https://www.ebi.ac.uk/biostudies/studies/S-EPMC11299996biostudies-literatureUnknown38(14)Limb-Girdle Muscular Dystrophy R1/2A (LGMD R1/2A) is caused by mutations in the CAPN3 gene encoding Calpain 3, a skeletal-muscle specific, Ca²⁺-dependent protease. Localization of Calpain 3 within the triad suggests it contributes to Ca²⁺ homeostasis. Through live-cell Ca²⁺ measurements, muscle mechanics, immunofluorescence, and electron microscopy (EM) in Capn3 deficient (C3KO) and wild-type (WT) mice, we determined whether loss of Calpain 3 altered Store-Operated Calcium Entry (SOCE) activity. Direct Ca²⁺ influx measurements revealed loss of Capn3 elicits elevated resting SOCE and increased resting cytosolic Ca²⁺, supported by high incidence of calcium entry units (CEUs) observed by EM. C3KO and WT mice were subjected to a single bouFASEB journal : official publication of the Federation of American Societies for Experimental BiologyLoss of Calpain 3 dysregulates store-operated calcium entry and its exercise response in mice.PMC11299996P50 AR052646AGR00024098Barton ERBoncompagni SWei-LaPierre LZhong RHenley-Beasley CSRastelli GHarris EVillani KRfalseLoss of Calpain 3 dysregulates store-operated calcium entry and its exercise response in mice.Limb-Girdle Muscular Dystrophy R1/2A (LGMD R1/2A) is caused by mutations in the CAPN3 gene encoding Calpain 3, a skeletal-muscle specific, Ca²⁺-dependent protease. Localization of Calpain 3 within the triad suggests it contributes to Ca²⁺ homeostasis. Through live-cell Ca²⁺ measurements, muscle mechanics, immunofluorescence, and electron microscopy (EM) in Capn3 deficient (C3KO) and wild-type (WT) mice, we determined whether loss of Calpain 3 altered Store-Operated Calcium Entry (SOCE) activity. Direct Ca²⁺ influx measurements revealed loss of Capn3 elicits elevated resting SOCE and increased resting cytosolic Ca²⁺, supported by high incidence of calcium entry units (CEUs) observed by EM. C3KO and WT mice were subjected to a single bou2024-01-01T00:00:00Z2024 Jul2026-03-16T08:59:58.561Z2025-08-15T03:06:42.313ZS-EPMC112999963903153210.1096/fj.202400697R10.1096/fj.202400697r