The M-cadherin catenin complex interacts with microtubules in skeletal muscle cells: implications for the fusion of myoblasts

M-cadherin, a calcium-dependent intercellular adhesion molecule, is express ed in skeletal muscle cells. Its pattern of expression, both in vivo and in cell culture as well as functional studies, have implied that M-cadherin i s important for skeletal muscle development, in particular the fusion of my oblasts into myotubes, M-cadherin formed complexes with the catenins in ske letal muscle cells similar to E-cadherin in epithelial cells, This suggeste d that the muscle-specific function of the M-cadherin catenin complex might be mediated by additional interactions with yet unidentified cellular comp onents, especially cytoskeletal elements, These include the microtubules wh ich also have been implicated in the fusion process of myoblasts. Here we p resent evidence that the M-cadherin catenin complex interacts with microtub ules in myogenic cells by using three independent experimental approaches, (1) Analysis by laser scan microscopy revealed that the destruction of micr otubules by nocodazole leads to an altered cell surface distribution of M-c adherin in differentiating myogenic cells. In contrast, disruption of actin filaments had little effect on the surface distribution of M-cadherin, (2) M-cadherin antibodies coimmunoprecipitated tubulin from extracts of nocoda zole-treated myogenic cells but not of nocodazole-treated epithelial cells ectopically expressing hl-cadherin. Vice versa, tubulin antibodies coimmuno precipitated M-cadherin from extracts of nocodazole-treated myogenic cells but not of nocodazole-treated M-cadherin-expressing epithelial cells, (3) M -cadherin and the catenins, but not a panel of control proteins, were copol ymerized with tubulin from myogenic cell extracts even after repeated cycle s of assembly and disassemly of tubulin, Moreover, neither M-cadherin nor E -cadherin could be found in a complex with microtubules in epithelial cells ectopically expressing M-cadherin, Our data are consistent with the idea t hat the interaction of M-cadherin with microtubules might be essential to k eep the myoblasts aligned during fusion, a process in which both M-cadherin and microtubules have been implicated.