A METALLOPROTEASE-DISINTEGRIN PARTICIPATING IN MYOBLAST FUSION

SKELETAL muscle development involves the formation of multinucleated m yotubes. This is thought to proceed by the induction of differentiatio n (acquisition of fusion competence) of myoblast cells, their aggregat ion, and union of their plasma membranes(1-3) Various membrane protein s including N-(4,5) and M-cadherins(6), N-(5,7-9) and V-CAMs(10) and i ntegrins(10,11) participate in myotube formation, but the molecular me chanisms of muscle cell fusion are poorly understood. Here we report t he identification of three new, myoblast-expressed gene products, mclt rin-alpha, beta and gamma, with homology to both viper haemorrhagic fa ctors(12,13) and fertilin (PH-30)(14,15), a membrane protein involved in egg-sperm fusion. Meltrin-alpha, a member of the metalloproteinase/ disintegrin protein family, appears to be required for myotube formati on. Involvement of a fertilin-related protein in myogenesis suggests t hat there are common mechanisms in gamete and myoblast fusion.