title: Cadherin-mediated adhesion is essential for myofibril continuity across the plasma membrane but not for assembly of the contractile apparatus.
abstract: 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.
authors.affiliation: Center for Research on Reproduction and Women's Health, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Luo
authors.forename: Glenn L
authors.initials: GL
authors.lastname: Radice
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000502:physiology*; D002450:Cell Communication / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism*; D048429:Cell Size / Q000502:physiology; D002478:Cells, Cultured; D018031:Connexin 43 / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D022001:Focal Adhesions / Q000502:physiology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D009200:Myocardial Contraction / Q000502:physiology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D009210:Myofibrils / Q000378:metabolism*
chemical_list: D015820:Cadherins; D018031:Connexin 43