The transport of prosaposin to lysosomes of epithelial cells lining the efferent ducts is impaired by the inactivation of the sortilin gene

摘要

Prosaposin is implicated in sphingolipid breakdown and sperm maturation. It is synthesized as a 53-kDa protein, post-translationally modified to a 65-kDa lysosomal form or glycosylated to a 70-kDa secretory isomer. Lysosomal prosaposin is the precursor of four saposins which are proteolytically cleaved in the lysosomes. Saposins are activator proteins for sphingolipid degradation by either solubilizing membrane sphingolipids or by forming complexes with specific enzymes and sphingolipid substrates. Most soluble lysosomal proteins traffic to lysosomes via the mannose 6-phosphate receptors (MPRs). However, prosaposin traffics with sortilin. Here we examine the effect of sortilin gene inactivation. Immunogold labeling with prosaposin antibody demonstrates that the inactivation decreases but does not abolish the transport of prosaposin to the lysosomes of epithelial cells lining the efferent ducts. These results suggest the existence of an alternative trafficking pathway for prosaposin.