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JCS ePress online publication date 25 Feb 2003
doi: 10.1242/jcs.00339

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Research Article

Cadherin-mediated adhesion is essential for myofibril continuity across the plasma membrane but not for assembly of the contractile apparatus


Yang Luo and Glenn L. Radice*
* Author for correspondence (e-mail: radice{at}mail.med.upenn.edu)

The strong coordinated contraction of heart muscle is dependent on the correct alignment and connection of the myofibrils across the plasma membrane. Previous studies indicate that N-cadherin is involved in cardiac myocyte adhesion and myofibrillogenesis. To investigate whether N-cadherin is specifically required for normal myocyte structure and function, we cultured myocytes from wild-type, N-cadherin-null and mutant embryos expressing the epithelial cadherin E-cadherin. In contrast to previous studies in chicken using N-cadherin-perturbing antibodies, our in vitro studies with mouse cells demonstrate that N-cadherin is not required for myofibrillogenesis, but is critical for myofibril organization. That is, N-cadherin-deficient myocytes beat and myofibrils were well formed; however, alignment of the myofibrils through regions of cell-cell contact was lost, resulting in their random orientation. Gap junctions were perturbed in the N-cadherin-null myocytes. By contrast, focal contacts appeared normal in the mutant cells. Furthermore, E-cadherin restored normal cell morphology and behavior to the N-cadherin-deficient myocytes, including proper alignment of the myofibrils. We conclude that a different adhesive system, most probably integrin, is responsible for myofibrillogenesis in the N-cadherin-null myocytes.
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