INVOLVEMENT OF M-CADHERIN IN TERMINAL DIFFERENTIATION OF SKELETAL-MUSCLE CELLS

Cadherins are a gene family encoding calcium-dependent cell adhesion p roteins which are thought to act in the establishment and maintenance of tissue organization. M-cadherin, one member of the family, has been found in myogenic cells of semitic origin during embryogenesis and in the adult, These findings have suggested that M-cadherin is involved in the regulation of morphogenesis of skeletal muscle cells, Therefore , we investigated the function of M-cadherin in the fusion of myoblast s into myotubes (terminal differentiation) in cell culture, Furthermor e, we tested whether M-cadherin might influence (a) the expression of troponin T, a typical marker of biochemical differentiation of skeleta l muscle cells, and (b) withdrawal of myoblasts from the cell cycle (c alled terminal commitment), The studies were performed by using antago nistic peptides which correspond to sequences of the putative M-cadher in binding domain, Analogous peptides of N-cadherin have previously be en shown to interfere functionally with the N-cadherin-mediated cell a dhesion, In the presence of antagonistic M-cadherin peptides, the fusi on of myoblasts into myotubes was inhibited. Analysis of troponin T re vealed that it was downregulated at the protein level although its mRN A was still detectable, In addition, withdrawal from the cell cycle ty pical for terminal commitment of muscle cells was not complete in fusi on-blocked myogenic cells, Finally, expression of M-cadherin antisense RNA reducing the expression of the endogenous M-cadherin protein inte rfered with the fusion process of myoblasts, Our data imply that M-cad herin-mediated myoblast interaction plays an important role in termina l differentiation of skeletal muscle cells.