{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T11:33:26Z","timestamp":1765280006783},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,7,13]],"date-time":"2017-07-13T00:00:00Z","timestamp":1499904000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,7,13]],"date-time":"2017-07-13T00:00:00Z","timestamp":1499904000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Transverse tubules (t-tubules) are uniquely-adapted membrane invaginations in cardiac myocytes that facilitate the synchronous release of Ca<jats:sup>2+<\/jats:sup> from internal stores and subsequent myofilament contraction, although these structures become disorganized and rarefied in heart failure. We previously observed that mitsugumin 29 (Mg29), an important t-tubule organizing protein in skeletal muscle, was induced in the mouse heart for the first time during dilated cardiomyopathy with heart failure. Here we generated cardiac-specific transgenic mice expressing Mg29 to model this observed induction in the failing heart. Interestingly, expression of Mg29 in the hearts of <jats:italic>Csrp3<\/jats:italic> null mice (encoding muscle LIM protein, MLP) partially restored t-tubule structure and preserved cardiac function as measured by invasive hemodynamics, without altering Ca<jats:sup>2+<\/jats:sup> spark frequency. Conversely, gene-deleted mice lacking both Mg29 and MLP protein showed a further reduction in t-tubule organization and accelerated heart failure. Thus, induction of Mg29 in the failing heart is a compensatory response that directly counteracts the well-characterized loss of t-tubule complexity and reduced expression of anchoring proteins such as junctophilin-2 (Jph2) that normally occur in this disease. Moreover, preservation of t-tubule structure by Mg29 induction significantly increases the function of the failing heart.<\/jats:p>","DOI":"10.1038\/s41598-017-05284-2","type":"journal-article","created":{"date-parts":[[2017,7,7]],"date-time":"2017-07-07T11:01:29Z","timestamp":1499425289000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Mitsugumin 29 regulates t-tubule architecture in the failing heart"],"prefix":"10.1038","volume":"7","author":[{"given":"Robert N.","family":"Correll","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey M.","family":"Lynch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tobias G.","family":"Schips","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vikram","family":"Prasad","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allen J.","family":"York","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle A.","family":"Sargent","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Didier X. P.","family":"Brochet","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianjie","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffery D.","family":"Molkentin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,7,13]]},"reference":[{"key":"5284_CR1","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.1161\/01.RES.0000135547.53927.F6","volume":"95","author":"F Brette","year":"2004","unstructured":"Brette, F., Salle, L. & Orchard, C. H. Differential modulation of L-type Ca2+ current by SR Ca2+ release at the T-tubules and surface membrane of rat ventricular myocytes. Circ. Res. \n                           95, e1\u20137 (2004).","journal-title":"Circ. 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