{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T13:07:02Z","timestamp":1784293622291,"version":"3.55.0"},"posted":{"date-parts":[[2024,1,15]]},"group-title":"Physiology","reference-count":42,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,1,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Limb-Girdle Muscular Dystrophy 2A (LGMD2A) is caused by mutations in the\n                  <jats:italic>CAPN3<\/jats:italic>\n                  gene encoding Calpain 3, a skeletal-muscle specific, Ca\n                  <jats:sup>2+<\/jats:sup>\n                  -dependent protease. Localization of Calpain 3 within the triad suggests it contributes to Ca\n                  <jats:sup>2+<\/jats:sup>\n                  homeostasis. Through live-cell Ca\n                  <jats:sup>2+<\/jats:sup>\n                  measurements, muscle mechanics, immunofluorescence, and electron microscopy (EM) in\n                  <jats:italic>Capn3<\/jats:italic>\n                  deficient (C3KO) and wildtype (WT) mice, we determined if loss of Calpain 3 altered Store-Operated Calcium Entry (SOCE) activity. Direct Ca\n                  <jats:sup>2+<\/jats:sup>\n                  influx measurements revealed loss of\n                  <jats:italic>Capn3<\/jats:italic>\n                  elicits elevated resting SOCE and increased resting cytosolic Ca\n                  <jats:sup>2+<\/jats:sup>\n                  , supported by high incidence of calcium entry units (CEUs) observed by EM. C3KO and WT mice were subjected to a single bout of treadmill running to elicit SOCE. Within 1HR post-treadmill running, C3KO mice exhibited diminished force production in\n                  <jats:italic>extensor digitorum longus<\/jats:italic>\n                  muscles and a greater decay of Ca\n                  <jats:sup>2+<\/jats:sup>\n                  transients in\n                  <jats:italic>flexor digitorum brevis<\/jats:italic>\n                  muscle fibers during repetitive stimulation. Striking evidence for impaired exercise-induced SOCE activation in C3KO mice included poor colocalization of key SOCE proteins, stromal-interacting molecule 1 (STIM1) and ORAI1, combined with disappearance of CEUs in C3KO muscles. These results demonstrate that Calpain 3 is a key regulator of SOCE in skeletal muscle and identify SOCE dysregulation as a contributing factor to LGMD2A pathology.\n                <\/jats:p>","DOI":"10.1101\/2024.01.12.575391","type":"posted-content","created":{"date-parts":[[2024,1,15]],"date-time":"2024-01-15T14:15:14Z","timestamp":1705328114000},"source":"Crossref","is-referenced-by-count":2,"title":["Loss of calpain 3 dysregulates store-operated calcium entry and its exercise response in mice"],"prefix":"10.64898","author":[{"given":"Katelyn R.","family":"Villani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renjia","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Spencer Henley-Beasley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgia","family":"Rastelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Boncompagni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7401-4398","authenticated-orcid":false,"given":"Elisabeth R.","family":"Barton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4781-5886","authenticated-orcid":false,"given":"Lan","family":"Wei-LaPierre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2024011719201546000_2024.01.12.575391v1.1","unstructured":"Angelini C . In: Adam MP , Mirzaa GM , Pagon RA , Wallace SE , Bean LJH , Gripp KW , et al. eds. GeneReviews \u00ae. 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