Mannose 6-phosphate receptors: potential mediators of germ cell-Sertoli cell interactions.

These studies have demonstrated that mouse pachytene spermatocytes, round spermatids, and Sertoli cells synthesize mannose 6-phosphate receptors and that the proportions of the CI- and CD-MPRs vary markedly between cell types. Isolated spermatogenic cells synthesize predominantly the CD-MPR and lower levels of the CI-MPR. In contrast, cultured Sertoli cells selectively synthesize the CI-MPR, even though transcripts for the CD-MPR have been detected in these cells. These striking differences in the expression of MPRs suggest that these receptors may serve multiple roles during germ cell differentiation. We have hypothesized that MPRs in the seminiferous epithelium mediate interactions between germ cells and Sertoli cells, and participate in the targeting of hydrolytic enzymes to the acrosome. In support of the first hypothesis, we have shown that functional MPRs are localized on the surface of spermatogenic cells and Sertoli cells where they mediate the endocytosis of M6P-containing ligands. As in other somatic cells, the CI-MPR is likely to be responsible for M6P receptor-mediated endocytosis in the seminiferous epithelium. Recent studies have shown that Sertoli cells in culture synthesize and secrete at least ten M6P-containing glycoproteins. Furthermore, pachytene spermatocytes and round spermatids endocytose these Sertoli M6P-glycoproteins and process them to lower molecular weight forms that persist during 17 h culture periods. The identification of relevant ligands for mannose 6-phosphate receptors in the seminiferous epithelium may help define new regulatory mechanisms in cell differentiation. Current efforts to determine if Sertoli M6P-glycoproteins modulate germ cell function should confirm the significance of surface MPRs and clarify their roles in signal transduction and/or the endocytosis of Sertoli cell products.