Prosaposin is immunolocalized to muscle and prosaptides promote myoblast fusion and attenuate loss of muscle mass after nerve injury

Prosaposin is the precursor of the saposins and has both neurotrophic and m yelinotrophic activity in vitro and in vivo. Using an antibody specific for the holoprotein, an immunocytochemical survey demonstrated intense stainin g of adult rat skeletal, cardiac, and smooth muscle cells. Prosaposin immun oreactivity in muscle appears dependent on innervation, as denervated adult rat skeletal muscles showed decreased immunostaining that returned to norm al levels after reinnervation. TX14(A), a peptide derived from the neurotro phic sequence of prosaposin, attenuated the decline in muscle mass loss fol lowing nerve injury induced by a constricting ligature. In vitro, both L6 m yoblasts and primary chick-embryo myoblasts showed similar prosaposin immun opositivity, mainly in myotubes. TX14(A) induced a threefold increase in L6 myoblast fusion during early stages of differentiation without affecting c ell proliferation. The fusion process was decreased in vitro in a dose-depe ndent fashion by addition of a neutralizing anti-prosaposin antibody. These data suggest that, in addition to neurotrophic and myelinotrophic activiti es, prosaposin has myotrophic properties. (C) 2001 John Wiley & Sons, Inc.