Sortilin knock‑down alters the expression and distribution of cathepsin D and prosaposin and up‑regulates the cation‑dependent mannose‑6‑phosphate receptor in rat epididymal cells

AGUILERA AC; LEIVA N; ALVAREZ P; PULCINI GEORGINA; PEREIRA LAURA; MORALES CR; SOSA MA; CARVELLI L

Scientific Reports

Springer

Año: 2023

2045-2322

The selective transport to lysosomes can be mediated by either mannose-6-phosphate receptors (CD-MPR and CI-MPR) or sortilin. In mammalian epididymis, some lysosomal proteins are secreted into the lumen through unknown mechanisms. To investigate the underlying mechanisms of lysosomal protein transport in epididymal cells we studied the expression and distribution of cathepsin D (CatD) and prosaposin (PSAP) in a stable sortilin knocked down RCE-1 epididymal cell line (RCE-1 KD) in comparison with non-transfected RCE-1 cells. In RCE-1 cells, sortilin was found to co-localize with CatD, whereas in RCE-1 KD cells, the expression, distribution and processing of the enzyme were altered. In turn, PSAP accumulated intracellularly upon sortilin knock-down and redistributed from LAMP-1positive compartment to a perinuclear location, remaining co-localized with CatD. Interestingly, the sortilin knock-down induced CD-MPR overexpression and a redistribution of the receptor from the perinuclear zone to a dispersed cytoplasmic location, accompanied by an increased co-localization with CatD. These findings suggest that CatD is transported to lysosomes by both the sortilin and the CD-MPR pathways and show the existence of an interplay between CD-MPR and sortilin in epididymal cells. The intracellular pathway taken by lysosomal proteins could explain the mechanism of exocytosis and therefore the role of these proteins in the epididymis.