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https://hdl.handle.net/2440/137374
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Type: | Journal article |
Title: | Actomyosin-mediated cellular tension promotes Yap nuclear translocation and myocardial proliferation through α5 integrin signaling |
Author: | Li, X. McLain, C. Samuel, M.S. Olson, M.F. Radice, G.L. |
Citation: | Development (Cambridge), 2023; 150(2):1-14 |
Publisher: | The Company of Biologists |
Issue Date: | 2023 |
ISSN: | 0950-1991 1477-9129 |
Statement of Responsibility: | Xiaofei Li, Callie McLain, Michael S. Samuel, Michael F. Olson, and Glenn L. Radic |
Abstract: | The 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. |
Keywords: | Rho-associated kinase; Nonmuscle myosin; Heart; Cardiomyocyte; Cell adhesion; Cadherin; Integrin; Adherens junctions; Focal adhesions; Fibronectin; Yap; Mouse |
Rights: | © 2023. Published by The Company of Biologists Ltd |
DOI: | 10.1242/dev.201013 |
Grant ID: | http://purl.org/au-research/grants/arc/FT120100132 |
Published version: | http://dx.doi.org/10.1242/dev.201013 |
Appears in Collections: | Medicine publications |
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