Roles of meltrin beta/ADAM19 in the processing of neuregulin

Meltrin beta /ADAM19 is a member of ADAMs (a disintegrin and metalloproteas es), which are a family of membrane-anchored glycoproteins that play import ant roles in fertilization, myoblast fusion, neurogenesis, and proteolytic processing of several membrane-anchored proteins. The expression pattern of meltrin beta during mouse development coincided well with that of neuregul in-1 (NRG), a member of the epidermal growth factor family. Then we examine d whether meltrin beta participates in the proteolytic processing of membra ne-anchored NRGs. When NRG-beta1 was expressed in mouse L929 cells, its ext racellular domain was constitutively processed and released into the cultur e medium. This basal processing activity was remarkably potentiated by over expression of wild-type meltrin beta, which lead to the significant decreas e in the cell surface exposure of extracellular domains of NRG-beta1. Furth ermore, expression of protease-deficient mutants of meltrin beta exerted do minant negative effects on the basal processing of NRG-beta1. These results indicate that meltrin beta participates in the processing of NRG-beta1. Si nce meltrin beta affected the processing of NRG-beta4 but not that of NRG-a lpha2, meltrin beta was considered to have a preference for beta -type NRGs as substrate. Furthermore, the effects of the secretory pathway inhibitors suggested that meltrin beta participates in the intracellular processing o f NRGs rather than the cleavage on the cell surface.