| Autor: |
Xiaofei Li, Callie McLain, Michael S. Samuel, Michael F. Olson, Glenn L. Radice |
| Přispěvatelé: |
Li, Xiaofei, McLain, Callie, Samuel, Michael S, Olson, Michael F, Radice, Glenn L |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Popis: |
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. Yet, the molecular mechanisms that regulate this critical developmental process are incompletely understood. 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. The Rho kinase (ROCK) serine/threonine protein kinases that act downstream of the RhoA small GTP-binding protein regulate nonmuscle myosin contractile force generation. To investigate the role of actomyosin contractility in cardiomyocyte maturation and cell cycle arrest, we conditionally-activated ROCK2 kinase domain (ROCK2:ER) in the murine postnatal heart. Here we show that cardiac-specific activation of actomyosin contractility shifts the balance from cell-cell to cell-matrix adhesions. Specifically, α5/β1 integrin and fibronectin matrix increase in response to actomyosin-mediated 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 increase intracellular tension by altering their intercellular contacts in favor of cell-matrix interactions leading to Yap nuclear translocation, thus uncovering a novel function for nonmuscle myosin contractility in promoting cardiomyocyte cell cycle activity in the postnatal heart. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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