α-Catenin localization and sarcomere self-organization on N-cadherin adhesive patterns are myocyte contractility driven.
The N-cadherin (N-cad) complex plays a crucial role in cardiac cell structure and function. Cadherins are adhesion proteins linking adjacent cardiac cells and, like integrin adhesions, are sensitive to force transmission. Forces through these adhesions are capable of eliciting structural and functional changes in myocytes. Compared to integrins, the mechanisms of force transduction through cadherins are less explored. α-catenin is a major component of the cadherin-catenin complex, thought to provide a link to the cell actin cytoskeleton. Using N-cad micropatterned substrates in an adhesion constrainment model, the results from this study show that α-catenin localizes to regions of highest internal stress in myocytes. This localization suggests that α-catenin acts as an adaptor protein associated with the cadherin mechanosensory apparatus, which is distinct from mechanosensing through integrins. Myosin inhibition in cells bound by integrins to fibronectin-coated patterns disrupts myofibiril organization, whereas on N-cad coated patterns, myosin inhibition leads to better organized myofibrils. This result indicates that the two adhesion systems provide independent mechanisms for regulating myocyte structural organization.
Department of Cardiothoracic Surgery, Drexel University College of Medicine, Philadelphia, Pennsylvania, United States of America.
Anant
A
Chopra
Akash
A
Patel
Adrian C
AC
Shieh
Paul A
PA
Janmey
J Yasha
JY
Kresh
D000199:Actins / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000378:metabolism* / Q000648:ultrastructure; D002448:Cell Adhesion; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003599:Cytoskeleton; D005353:Fibronectins / Q000378:metabolism; D016023:Integrins / Q000378:metabolism; D009119:Muscle Contraction / Q000502:physiology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure; D009210:Myofibrils / Q000378:metabolism; D009218:Myosins / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D012518:Sarcomeres / Q000378:metabolism / Q000648:ultrastructure; D051178:alpha Catenin / Q000378:metabolism / Q000648:ultrastructure; D051176:beta Catenin / Q000378:metabolism
D000199:Actins; D015820:Cadherins; D003598:Cytoskeletal Proteins; D005353:Fibronectins; D016023:Integrins; D051178:alpha Catenin; D051176:beta Catenin; D009218:Myosins