{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:11:42Z","timestamp":1768522302056,"version":"3.49.0"},"posted":{"date-parts":[[2025,6,11]]},"group-title":"Molecular Biology","reference-count":13,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T00:00:00Z","timestamp":1749600000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["2R15AR068583-02"],"award-info":[{"award-number":["2R15AR068583-02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,6,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Duchenne muscular dystrophy (DMD) involves progressive muscle degeneration associated with calcium dysregulation, but the mechanisms linking extracellular matrix (ECM) integrity to calcium homeostasis remain unclear. We investigated whether MUA- 3, a fibrillin-related ECM protein in\n                  <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                  , contributes to calcium regulation in dystrophic muscle. Using fluorescent calcium imaging in transgenic worms expressing muscle-specific GCaMP2, we found that downregulating\n                  <jats:italic>mua-3<\/jats:italic>\n                  selectively elevated resting calcium levels in healthy muscle but had no effect in dystrophic (\n                  <jats:italic>dys-1<\/jats:italic>\n                  ) muscle, suggesting impaired MUA-3 function in dystrophy. Despite altered calcium dynamics,\n                  <jats:italic>mua-3<\/jats:italic>\n                  downregulation did not affect locomotor function. In human dystrophic myoblasts, we observed significantly elevated sarcoplasmic calcium levels concurrent with substantial downregulation of fibrillin genes FBN1\/FBN2. These findings demonstrate that fibrillin-related proteins regulate calcium homeostasis across species, suggesting that ECM integrity directly contributes to cellular calcium control in muscle. This work identifies a conserved mechanism linking extracellular matrix stability to intracellular calcium regulation and suggests that targeting ECM-calcium coupling may offer new therapeutic approaches for muscular dystrophy.\n                <\/jats:p>","DOI":"10.1101\/2025.06.09.658655","type":"posted-content","created":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T21:30:15Z","timestamp":1749677415000},"source":"Crossref","is-referenced-by-count":0,"title":["Fibrillin-Related Proteins Control Calcium Homeostasis in Dystrophic Muscle Across Species"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-9157-1561","authenticated-orcid":false,"given":"D","family":"Marchiafava","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5981-5528","authenticated-orcid":false,"given":"AG","family":"Vidal-Gadea","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2025061317302324000_2025.06.09.658655v1.1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00007.2015"},{"key":"2025061317302324000_2025.06.09.658655v1.2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200103035"},{"key":"2025061317302324000_2025.06.09.658655v1.3","doi-asserted-by":"publisher","DOI":"10.1051\/medsci\/20031967725"},{"key":"2025061317302324000_2025.06.09.658655v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/nature12354"},{"key":"2025061317302324000_2025.06.09.658655v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2012.07.023"},{"key":"2025061317302324000_2025.06.09.658655v1.6","doi-asserted-by":"crossref","unstructured":"Duan, D. , Goemans, N. , Takeda, S. , Mercuri, E. , & Aartsma-Rus, A. Duchenne muscular dystrophy. Nature Reviews Disease Primers, 7(1), 13.","DOI":"10.1038\/s41572-021-00248-3"},{"key":"2025061317302324000_2025.06.09.658655v1.7","doi-asserted-by":"publisher","DOI":"10.1534\/g3.115.018465"},{"key":"2025061317302324000_2025.06.09.658655v1.8","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2007-8-9-r188"},{"key":"2025061317302324000_2025.06.09.658655v1.9","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1811379116"},{"key":"2025061317302324000_2025.06.09.658655v1.10","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.647010"},{"key":"2025061317302324000_2025.06.09.658655v1.11","doi-asserted-by":"publisher","DOI":"10.1038\/84397"},{"key":"2025061317302324000_2025.06.09.658655v1.12","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-009-0822-x"},{"key":"2025061317302324000_2025.06.09.658655v1.13","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2089"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.06.09.658655","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T08:54:24Z","timestamp":1768467264000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.06.09.658655"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,11]]},"references-count":13,"URL":"https:\/\/doi.org\/10.1101\/2025.06.09.658655","relation":{},"subject":[],"published":{"date-parts":[[2025,6,11]]},"subtype":"preprint"}}