Actomyosin-mediated cellular tension promotes Yap nuclear translocation and myocardial proliferation through α5 integrin signaling

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dc.contributor.authorLi, X.
dc.contributor.authorMcLain, C.
dc.contributor.authorSamuel, M.S.
dc.contributor.authorOlson, M.F.
dc.contributor.authorRadice, G.L.
dc.date.issued2023
dc.description.abstractThe cardiomyocyte phenotypic switch from a proliferative to terminally differentiated state results in the loss of regenerative potential of the mammalian heart shortly after birth. Nonmuscle myosin IIB (NM IIB)-mediated actomyosin contractility regulates cardiomyocyte cytokinesis in the embryonic heart, and NM IIB levels decline after birth, suggesting a role for cellular tension in the regulation of cardiomyocyte cell cycle activity in the postnatal heart. To investigate the role of actomyosin contractility in cardiomyocyte cell cycle arrest, we conditionally activated ROCK2 kinase domain (ROCK2:ER) in the murine postnatal heart. Here, we show that α5/β1 integrin and fibronectin matrix increase in response to actomyosinmediated tension. Moreover, activation of ROCK2:ER promotes nuclear translocation of Yap, a mechanosensitive transcriptional co-activator, and enhances cardiomyocyte proliferation. Finally, we show that reduction of myocardial α5 integrin rescues the myocardial proliferation phenotype in ROCK2:ER hearts. These data demonstrate that cardiomyocytes respond to increased intracellular tension by altering their intercellular contacts in favor of cell–matrix interactions, leading to Yap nuclear translocation, thus uncovering a function for nonmuscle myosin contractility in promoting cardiomyocyte proliferation in the postnatal heart.
dc.description.statementofresponsibilityXiaofei Li, Callie McLain, Michael S. Samuel, Michael F. Olson, and Glenn L. Radic
dc.identifier.citationDevelopment, 2023; 150(2):1-14
dc.identifier.doi10.1242/dev.201013
dc.identifier.issn0950-1991
dc.identifier.issn1477-9129
dc.identifier.orcidSamuel, M.S. [0000-0001-7880-6379]
dc.identifier.urihttps://hdl.handle.net/2440/137374
dc.language.isoen
dc.publisherThe Company of Biologists
dc.relation.granthttp://purl.org/au-research/grants/arc/FT120100132
dc.rights© 2023. Published by The Company of Biologists Ltd
dc.source.urihttps://doi.org/10.1242/dev.201013
dc.subjectRho-associated kinase; Nonmuscle myosin; Heart; Cardiomyocyte; Cell adhesion; Cadherin; Integrin; Adherens junctions; Focal adhesions; Fibronectin; Yap; Mouse
dc.subject.meshMyocytes, Cardiac
dc.subject.meshAnimals
dc.subject.meshMammals
dc.subject.meshMice
dc.subject.meshActomyosin
dc.subject.meshIntegrin alpha5
dc.subject.meshTranscription Factors
dc.subject.meshCell Proliferation
dc.subject.meshActin Cytoskeleton
dc.titleActomyosin-mediated cellular tension promotes Yap nuclear translocation and myocardial proliferation through α5 integrin signaling
dc.typeJournal article
pubs.publication-statusPublished online

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