Role of sulfated glycoprotein‐1 (SGP‐1) in the disposal of residual bodies by sertoli cells of the rat

Abstract

Sulfated glycoprotein-1 (SGP-1) is a polypeptide secreted by Sertoli cells in the rat. Sequence analysis revealed a 76% sequence similarity with human prosaposin produced by various cell types. Human prosaposin is a 70 kDa protein which is cleaved in the lysosomes into four 10-15 kDa polypeptides termed saposins A, B, C, and D. The function of lysosomal saposins is to either solubilize certain membrane glycolipids or to form complexes with lysosomal enzymes and/or their glycolipid substrate to facilitate their hydrolysis. The present investigation dealt with the delivery of SGP-1 into the phagosomes of Sertoli cells; these phagosomes contain the residual bodies which detach from the late spermatids at the time of spermiation. Immunogold labeling with anti-SGP-1 antibody was found over Sertoli cell lysosomes, but was absent from phagosomes formed after phagocytosis of spermatid residual bodies in the apical Sertoli cell cytoplasm in stages VIII and early IX of the cycle of the seminiferous epithelium. The phagosomes found later in the basal Sertoli cell cytoplasm in stages IX and X of the cycle became labeled with the antibody as the components of the residual bodies rapidly underwent lysis and disappeared from the Sertoli cells. Sertoli cell lysosomes isolated by cell fractionation (estimated purity of 80%) were found to contain a 65 kDa form of SGP-1 or prosaposin, as well as the 15 kDa polypeptides or saposins. Thus, it appears that this unique lysosomal form of SGP-1 reached the Sertoli cell phagosomes and that their derived polypeptides, the saposins, must play a role in the hydrolysis of membrane glycolipids found in phagocytosed residual bodies.

Differential expression of cathepsins B and D in testis and epididymis of adult rats.

“…A similar pattern of immunolabeling has also been reported for sulfated glycoprotein-1 (SGP-1). Although seen in lysosomes by elec- .... tron microscopy, SGP-1 has also been reported to be secreted into the lumen, accounting for the diffuse cytoplasmic reaction as seen in the light microscope (Igdoura and Morales, 1995;Collard et al, 1988).…”

The Lysosomal Transport of Prosaposin Requires the Conditional Interaction of Its Highly Conserved D Domain with Sphingomyelin

“…Saposins A, B, C, and D are four activators derived from partial proteolysis of a common precursor, prosaposin (13). Studies in our laboratory demonstrated the existence of two forms of prosaposin, a lysosomal isomer (65 kDa) and a secreted form (70 kDa) found in extracellular fluids (10,27). Genetic deficiency of lysosomal prosaposin leads to an accumulation of undigested sphingolipids in the lysosomes (13).…”

“…*, values statistically different according to Student's t test. (6,10,27). The use of inhibitors of sphingolipid synthesis, PDMP, FB 1 , and D609 suggested that prosaposin does not depend on GSLs but on sphingomyelin for its transport to the lysosomal compartment (21).…”

“…In this investigation we used an additional model system, the seminiferous tubules from the mouse testes, to verify the role of sphingomyelin in the targeting of prosaposin to the lysosomes. Sertoli cells, the somatic components of the seminiferous epithelium lining these tubules, are professional phagocytes that have large amounts of lysosomes containing endogenous prosaposin (27). Using a similar experimental approach (i.e.…”

“…In this model system two cell types are present, the germinal cells and the Sertoli cells. Sertoli cells are the somatic components of the seminiferous tubules, which have lysosomes containing prosaposin (27). Immunogold labeling of seminiferous tubules with the ␣-prosaposin antibody specifically labeled the lysosomes of Sertoli cells (Fig.…”