{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T07:47:32Z","timestamp":1790063252954,"version":"4.0.1"},"reference-count":56,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T00:00:00Z","timestamp":1726444800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T00:00:00Z","timestamp":1726444800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["23TPA1074093"],"award-info":[{"award-number":["23TPA1074093"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["2312925"],"award-info":[{"award-number":["2312925"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000015","name":"U.S. Department of Energy","doi-asserted-by":"publisher","award":["DE\u2010AC02\u201006CH11357"],"award-info":[{"award-number":["DE\u2010AC02\u201006CH11357"]}],"id":[{"id":"10.13039\/100000015","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      Precise regulation of sarcomeric contraction is essential for normal cardiac function. The heart must generate sufficient force to pump blood throughout the body, but either inadequate or excessive force can lead to dysregulation and disease. Myosin regulatory light chain (RLC) is a thick\u2010filament protein that binds to the neck of the myosin heavy chain. Post\u2010translational phosphorylation of RLC (RLC\u2010P) by myosin light chain kinase is known to influence acto\u2010myosin interactions, thereby increasing force production and Ca\n                      <jats:sup>2+<\/jats:sup>\n                      \u2010sensitivity of contraction. Here, we investigated the role of RLC\u2010P on cardiac structure and function as sarcomere length and [Ca\n                      <jats:sup>2+<\/jats:sup>\n                      ] were altered. We found that at low, non\u2010activating levels of Ca\n                      <jats:sup>2+<\/jats:sup>\n                      , RLC\u2010P contributed to myosin head disorder, though there were no effects on isometric stress production and viscoelastic stiffness. With increases in sarcomere length and Ca\n                      <jats:sup>2+<\/jats:sup>\n                      \u2010activation, the structural changes due to RLC\u2010P become greater, which translates into greater force production, greater viscoelastic stiffness, slowed myosin detachment rates and altered nucleotide handling. Altogether, these data suggest that RLC\u2010P may alter thick\u2010filament structure by releasing ordered, off\u2010state myosin. These more disordered myosin heads are available to bind actin, which could result in greater force production as Ca\n                      <jats:sup>2+<\/jats:sup>\n                      levels increase. However, prolonged cross\u2010bridge attachment duration due to slower ADP release could delay relaxation long enough to enable cross\u2010bridge rebinding. Together, this work further elucidates the effects of RLC\u2010P in regulating muscle function, thereby promoting a better understanding of thick\u2010filament regulatory contributions to cardiac function in health and disease.\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp16309-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Myosin regulatory light chain (RLC) is a thick\u2010filament protein in the cardiac sarcomere that can be phosphorylated (RLC\u2010P), and changes in RLC\u2010P are associated with cardiac dysfunction and disease.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>This study assesses how RLC\u2010P alters cardiac muscle structure and function at different sarcomere lengths and calcium concentrations.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            At low, non\u2010activating levels of Ca\n                            <jats:sup>2+<\/jats:sup>\n                            , RLC\u2010P contributed to myofilament disorder, though there were no effects on isometric stress production and viscoelastic stiffness.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            With increases in sarcomere length and Ca\n                            <jats:sup>2+<\/jats:sup>\n                            \u2010activation, the structural changes due to RLC\u2010P become greater, which translates into greater force production, greater viscoelastic stiffness, slower myosin detachment rate and altered cross\u2010bridge nucleotide handling rates.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>This work elucidates the role of RLC\u2010P in regulating muscle function and facilitates understanding of thick\u2010filament regulatory protein contributions to cardiac function in health and disease.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp286802","type":"journal-article","created":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T14:19:28Z","timestamp":1726496368000},"page":"4941-4958","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The structural and functional effects of myosin regulatory light chain phosphorylation are amplified by increases in sarcomere length and [Ca\n                    <sup>2+<\/sup>\n                    ]"],"prefix":"10.1113","volume":"602","author":[{"given":"Kyrah L.","family":"Turner","sequence":"first","affiliation":[{"name":"School of Molecular Biosciences Washington State University  Pullman WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blake J.","family":"Vander Top","sequence":"additional","affiliation":[{"name":"Department of Integrative Physiology and Neuroscience Washington State University  Pullman WA 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