Vinculin Anchors Contractile Actin to the Cardiomyocyte Adherens Junction
Overview
Molecular Biology
Affiliations
The adherens junction (AJ) couples the actin cytoskeletons of neighboring cells to allow mechanical integration and tissue organization. The physiological demands of intercellular adhesion require that the AJ be responsive to dynamic changes in force while maintaining mechanical load. These demands are tested in the heart, where cardiomyocyte AJs must withstand repeated cycles of actomyosin-mediated contractile force. Here we show that force-responsive cardiomyocyte AJs recruit actin-binding ligands to selectively couple actin networks. We employed a panel of N-cadherin-αE-catenin fusion proteins to rebuild AJs with specific actin linkages in N-cadherin-null cardiomyocytes. In this system, vinculin recruitment was required to rescue myofibril integration at nascent contacts. In contrast, loss of vinculin from the AJ disrupted junction morphology and blocked myofibril integration at cell-cell contacts. Our results identify vinculin as a critical link to contractile actomyosin and offer insight to how actin integration at the AJ is regulated to provide stability under mechanical load.
DePalma S, Jilberto J, Stis A, Huang D, Lo J, Davidson C Adv Sci (Weinh). 2024; 11(47):e2309740.
PMID: 39558513 PMC: 11653763. DOI: 10.1002/advs.202309740.
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Morikawa Y, Kim J, Li R, Liu L, Liu S, Deshmukh V Circulation. 2024; 151(1):76-93.
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Callaway D, Nicholl I, Shi B, Reyes G, Farago B, Bu Z Proc Natl Acad Sci U S A. 2024; 121(39):e2408459121.
PMID: 39298480 PMC: 11441495. DOI: 10.1073/pnas.2408459121.
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Mezher M, Dumbali S, Fenn I, Lamb C, Miller C, Sharmin S Biophys J. 2024; 122(23):4518-4527.
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Ng R, Gokhan I, Stankey P, Akar F, Campbell S Am J Physiol Heart Circ Physiol. 2023; .
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