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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2024,5,28]]},"abstract":"<jats:p>\n                    Maintaining the structure of cardiac membranes and membrane organelles is essential for heart function. A critical cardiac membrane organelle is the transverse tubule system (called the t-tubule system) which is an invagination of the surface membrane. A unique structural characteristic of the cardiac muscle t-tubule system is the extension of the extracellular matrix (ECM) from the surface membrane into the t-tubule lumen. However, the importance of the ECM extending into the cardiac t-tubule lumen is not well understood. Dystroglycan (DG) is an ECM receptor in the surface membrane of many cells, and it is also expressed in t-tubules in cardiac muscle. Extensive posttranslational processing and\n                    <jats:italic>O<\/jats:italic>\n                    -glycosylation are required for DG to bind ECM proteins and the binding is mediated by a glycan structure known as matriglycan. Genetic disruption resulting in defective\n                    <jats:italic>O<\/jats:italic>\n                    -glycosylation of DG results in muscular dystrophy with cardiorespiratory pathophysiology. Here, we show that DG is essential for maintaining cardiac t-tubule structural integrity. Mice with defects in\n                    <jats:italic>O<\/jats:italic>\n                    -glycosylation of DG developed normal t-tubules but were susceptible to stress-induced t-tubule loss or severing that contributed to cardiac dysfunction and disease progression. Finally, we observed similar stress-induced cardiac t-tubule disruption in a cohort of mice that solely lacked matriglycan. Collectively, our data indicate that DG in t-tubules anchors the luminal ECM to the t-tubule membrane via the polysaccharide matriglycan, which is critical to transmitting structural strength of the ECM to the t-tubules and provides resistance to mechanical stress, ultimately preventing disruptions in cardiac t-tubule integrity.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2402890121","type":"journal-article","created":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T13:47:30Z","timestamp":1716299250000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":12,"title":["Matriglycan maintains t-tubule structural integrity in cardiac muscle"],"prefix":"10.1073","volume":"121","author":[{"given":"Jeffrey M.","family":"Hord","sequence":"first","affiliation":[{"name":"HHMI, University of Iowa, Iowa City, IA 52242"},{"name":"Senator Paul D. Wellstone Muscular Dystrophy Specialized Research Center, University of Iowa, Iowa City, IA 52242"},{"name":"Department of Molecular Physiology and Biophysics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242"},{"name":"Department of Neurology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary E.","family":"Anderson","sequence":"additional","affiliation":[{"name":"HHMI, University of Iowa, Iowa City, IA 52242"},{"name":"Senator Paul D. Wellstone Muscular Dystrophy Specialized Research Center, University of Iowa, Iowa City, IA 52242"},{"name":"Department of Molecular Physiology and Biophysics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242"},{"name":"Department of Neurology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally J.","family":"Prouty","sequence":"additional","affiliation":[{"name":"HHMI, University of Iowa, Iowa City, IA 52242"},{"name":"Senator Paul D. Wellstone Muscular Dystrophy Specialized Research Center, University of Iowa, Iowa City, IA 52242"},{"name":"Department of Molecular Physiology and Biophysics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242"},{"name":"Department of Neurology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shelly","family":"Melton","sequence":"additional","affiliation":[{"name":"HHMI, University of Iowa, Iowa City, IA 52242"},{"name":"Senator Paul D. Wellstone Muscular Dystrophy Specialized Research Center, University of Iowa, Iowa City, IA 52242"},{"name":"Department of Molecular Physiology and Biophysics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242"},{"name":"Department of Neurology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeita","family":"Gastel","sequence":"additional","affiliation":[{"name":"HHMI, University of Iowa, Iowa City, IA 52242"},{"name":"Senator Paul D. Wellstone Muscular Dystrophy Specialized Research Center, University of Iowa, Iowa City, IA 52242"},{"name":"Department of Molecular Physiology and Biophysics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242"},{"name":"Department of Neurology, Roy J. and Lucille A. 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