{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T05:58:29Z","timestamp":1733983109903,"version":"3.30.2"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T00:00:00Z","timestamp":1727222400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100020950","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["MOST 104\u20102320\u2010B\u2010002\u2010053\u2010MY3","MOST 107\u20102320\u2010B\u2010002\u2010012\u2010MY3","MOST 110\u20102320\u2010B\u2010002\u2010052\u2010MY3","MOST 111\u20102320\u2010B\u2010002\u2010077\u2010MY3","National Health Research Institute","NHRI\u2010105\u20101053ISI"],"award-info":[{"award-number":["MOST 104\u20102320\u2010B\u2010002\u2010053\u2010MY3","MOST 107\u20102320\u2010B\u2010002\u2010012\u2010MY3","MOST 110\u20102320\u2010B\u2010002\u2010052\u2010MY3","MOST 111\u20102320\u2010B\u2010002\u2010077\u2010MY3","National Health Research Institute","NHRI\u2010105\u20101053ISI"]}],"id":[{"id":"10.13039\/501100020950","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Nuclear receptor interaction protein (NRIP) is versatile and engages with various proteins to execute its diverse biological function. NRIP deficiency was reported to cause small myofibre size in adult muscle regeneration, indicating a crucial role of NRIP in myoblast fusion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The colocalization and interaction of NRIP with actin were investigated by immunofluorescence and immunoprecipitation assay, respectively. The participation of NRIP in myoblast fusion was demonstrated by cell fusion assay and time\u2010lapse microscopy. The NRIP mutants were generated for mechanism study in NRIP\u2010null C2C12 (termed KO19) cells and muscle\u2010specific NRIP knockout (NRIP cKO) mice. A GEO profile database was used to analyse NRIP expression in Duchenne muscular dystrophy (DMD) patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In this study, we found that NRIP directly and reciprocally interacted with actin both in\u00a0vitro and in cells. Immunofluorescence microscopy showed that the endogenous NRIP colocalized with components of invadosome, such as actin, Tks5, and cortactin, at the tips of cells during C2C12 differentiation. The KO19 cells were generated and exhibited a significant deficit in myoblast fusion compared with wild\u2010type C2C12 cells (3.16% vs. 33.67%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.005). Overexpressed NRIP in KO19 cells could rescue myotube formation compared with control (3.37% vs. 1.00%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01). We further confirmed that NRIP directly participated in cell fusion by using a cell\u2013cell fusion assay. We investigated the mechanism of invadosome formation for myoblast fusion, which depends on NRIP\u2013actin interaction, by analysing NRIP mutants in NRIP\u2010null cells. Loss of actin\u2010binding of NRIP reduced invadosome (enrichment ratio, 1.00 vs. 2.54, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01) and myotube formation (21.82% vs. 35.71%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) in KO19 cells and forced NRIP expression in KO19 cells and muscle\u2010specific NRIP knockout (NRIP cKO) mice increased myofibre size compared with controls (over 1500\u2009\u03bcm<jats:sup>2<\/jats:sup>, 61.01% vs. 20.57%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). We also found that the NRIP mRNA level was decreased in DMD patients compared with healthy controls (18\u2009072 vs. 28\u2009289, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001, <jats:italic>N<\/jats:italic>\u2009=\u200910 for both groups).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>NRIP is a novel actin\u2010binding protein for invadosome formation to induce myoblast fusion.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.13598","type":"journal-article","created":{"date-parts":[[2024,9,26]],"date-time":"2024-09-26T05:25:59Z","timestamp":1727328359000},"page":"2559-2573","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Innovative Role of Nuclear Receptor Interaction Protein in Orchestrating Invadosome Formation for Myoblast Fusion"],"prefix":"10.1002","volume":"15","author":[{"given":"Hsin\u2010Hsiung","family":"Chen","sequence":"first","affiliation":[{"name":"Graduate Institute of Microbiology, College of Medicine National Taiwan University  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chia\u2010Yang","family":"Lin","sequence":"additional","affiliation":[{"name":"Graduate Institute of Microbiology, College of Medicine National Taiwan University  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ya\u2010Ju","family":"Han","sequence":"additional","affiliation":[{"name":"Graduate Institute of Microbiology, College of Medicine National Taiwan University  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun\u2010Hsin","family":"Huang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Microbiology, College of Medicine National Taiwan University  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi\u2010Hsiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Graduate Institute of Microbiology, College of Medicine National Taiwan University  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wan\u2010En","family":"Hsu","sequence":"additional","affiliation":[{"name":"Graduate Institute of Microbiology, College of Medicine National Taiwan University  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li\u2010Kai","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Neurology National Taiwan University Hospital  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsing\u2010Jung","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Neurology National Taiwan University Hospital  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yeou\u2010Ping","family":"Tsao","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Mackay Memorial Hospital  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsiang\u2010Po","family":"Huang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Medical Genomics and Proteomics, College of Medicine National Taiwan University  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6588-8632","authenticated-orcid":false,"given":"Show\u2010Li","family":"Chen","sequence":"additional","affiliation":[{"name":"Graduate Institute of Microbiology, College of Medicine National Taiwan University  Taipei 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