Biology of Reproduction, Vol 55, 676-683, Copyright © 1996 by Society for the Study of Reproduction

ARTICLES

Low density lipoprotein receptor-related protein-2 expression in efferent duct and epididymal epithelia: evidence in rats for its in vivo role in endocytosis of apolipoprotein J/clusterin

CR Morales, SA Igdoura, UA Wosu, J Boman and WS Argraves
Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada. cxco@musica.mcgill.ca

Apolipoprotein J/clusterin/sulfated glycoprotein-2 (apo J) disassociates from spermatozoa and is endocytosed by epithelial cells lining the efferent ducts and epididymis. The low density lipoprotein receptor-related protein-2/megalin (LRP-2) has been shown to bind to apo J and mediates its endocytosis and lysosomal degradation in cultured cells. In this study, immunocytological techniques were used to localize LRP-2 in rat efferent ducts and epididymis and to determine whether its expression correlated with those epithelial cells involved in apo J endocytosis. Pronounced LRP-2 immunochemical staining was observed on the apical surfaces of epithelial cells lining the efferent ducts and in the intermediate zone, proximal caput, and corpus and cauda regions of the epididymis. Single immunogold labeling at the electron microscopic level showed LRP-2 to be present within coated pits, endocytic vesicles, and early endosomes of the nonciliated cells of the efferent ducts and the principal cells of the epididymis. In efferent ducts, double immunogold labeling showed both LRP-2 and apo J to be present in endocytic compartments including coated pits, endocytic vesicles, and early endosomes of nonciliated cells. However, while apo J was detected in late endosomes and lysosomes of nonciliated cells, LRP-2 was not. Apical tubules, possibly emerging from late endosomes, contained labeling for LRP-2 but not for apo J. Ciliated cells lying adjacent to nonciliated cells displayed no labeling for either LRP-2 or apo J. These results are consistent with the possibility that LRP-2 serves as an endocytic receptor for apo J in vivo and that after endocytosis the LRP-2 is recycled back to the cell surface while apo J is delivered to the lysosomes for degradation. To provide additional evidence implicating LRP-2 in apo J endocytosis, a receptor-associated protein (RAP), an antagonist of apo J binding to LRP-2, was injected into the efferent duct lumen. Subsequent immunocytological analysis of the efferent duct showed that the RAP treatment abolished the endocytosis of apo J by the nonciliated cells. Taken together, these data indicate that LRP-2 is a likely mediator of apo J endocytosis by the nonciliated efferent duct cells.

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