{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T07:06:22Z","timestamp":1779433582569,"version":"3.53.1"},"reference-count":34,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01\u2010HL178582"],"award-info":[{"award-number":["R01\u2010HL178582"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006519","name":"Edna and Fred L. Mandel, Jr. Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006519","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Physiological Reports"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Sarcomeres are the fundamental contractile units of muscle. Despite their importance, sarcomere assembly remains poorly understood. We focused on Actn2, a protein which stabilizes the sarcomere by linking proteins to the Z\u2010disk. During C2C12 differentiation into myoblasts, Actn2 protein levels remained constant. This finding suggested that Actn2 incorporation into the sarcomere arose from a post\u2010translational mechanism. We hypothesized that the post\u2010translational mechanism relied on phosphorylation. Alignment of Actn2 protein sequences from animals with three\u2010 or four\u2010chambered hearts identified a conserved sequence, T\n                    <jats:sup>308<\/jats:sup>\n                    P\n                    <jats:sup>309<\/jats:sup>\n                    E\n                    <jats:sup>310<\/jats:sup>\n                    K\n                    <jats:sup>311<\/jats:sup>\n                    , that matches the consensus phosphorylation motif of the cell\u2010cycle kinase CDK1. In\u00a0vitro kinase assays showed that CDK1 phosphorylates Actn2 at T308. In contrast, CDK1 was unable to phosphorylate Actn2 when T308 was mutated to alanine (T308A). Using CRISPR\u2010Cas9 gene editing, we created Actn2\u2010T308A and phosphomimetic Actn2\u2010T308D variants in C2C12 cells. C2C12 cells expressing Actn2\u2010T308A differentiated rapidly and formed robust sarcomeres. However, C2C12 cells expressing Actn2\u2010T308D failed to form organized sarcomeres. Curiously, Actn2\u2010T308A cells were found to have less proliferative capacity than Actn2\u2010T308D cells. Taken together, these results identify CDK1\u2010dependent phosphorylation of Actn2\u2010T308 as being important for sarcomere assembly. Moreover, the data also suggest a mechanism by which cell\u2010cycle exit promotes sarcomere assembly.\n                  <\/jats:p>","DOI":"10.14814\/phy2.70826","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T08:37:21Z","timestamp":1775723841000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cell\u2010cycle regulation of sarcomere integrity\u2014Role for Actn2 phosphorylation"],"prefix":"10.14814","volume":"14","author":[{"given":"S. S.","family":"Baksh","sequence":"first","affiliation":[{"name":"Mandel Center for Heart and Vascular Research, and the Duke Cardiovascular Research Center Duke University Medical Center  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Anwar","sequence":"additional","affiliation":[{"name":"Mandel Center for Heart and Vascular Research, and the Duke Cardiovascular Research Center Duke University Medical Center  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X.","family":"Wang","sequence":"additional","affiliation":[{"name":"Mandel Center for Heart and Vascular Research, and the Duke Cardiovascular Research Center Duke University Medical Center  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. E.","family":"Pratt","sequence":"additional","affiliation":[{"name":"Mandel Center for Heart and Vascular Research, and the Duke Cardiovascular Research Center Duke University Medical Center  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V. J.","family":"Dzau","sequence":"additional","affiliation":[{"name":"Mandel Center for Heart and Vascular Research, and the Duke Cardiovascular Research Center Duke University Medical Center  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6460-7333","authenticated-orcid":false,"given":"C. P.","family":"Hodgkinson","sequence":"additional","affiliation":[{"name":"Mandel Center for Heart and Vascular Research, and the Duke Cardiovascular Research Center Duke University Medical Center  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,9]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.04.060"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.85008"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3149"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0129176"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2103676118"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0955-0674(99)80003-9"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-60236-x"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2022.837611"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2018.08.024"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-31144-3"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2015.06.002"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2022.972301"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/bies.200900110"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiomech.2023.111553"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cdev.2021.203760"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12054"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2020.08.018"},{"key":"e_1_2_11_19_1","first-page":"449","article-title":"Acute Exercise Modifies Titin Phosphorylation and Increases Cardiac Myofilament Stiffness","volume":"5","author":"Muller A. 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