Identification of cubilin (p400) as galectin-3 binding protein from the murine utero-placental complex

Date

2000-12

Journal Title

Journal ISSN

Volume Title

Publisher

Texas Tech University

Abstract

Galectin-3 is a soluble p-galactoside binding lectin that is present in several cell types within the uteroplacental complex (UPC) of mice. Affinity chromatography with immobilized galectin-3 was used to isolate potential binding partners for the lectin from homogenates of UPC. At least one glycoprotein (Mr 400,000; p400) was isolated that bound galectin-3 in a carbohydrate-dependent manner. Exposure of p400 to glycosidases decreased its apparent size by 10%. Differential migration of p400 in nonreducing and reducing conditions demonstrated that the protein contains intramolecular disulfide bonds. Amino acid sequencing revealed similarity to cubilin, a 400 kDa endocytic receptor. Collectively, the molecular size of p400, its degree of glycosylation, the presence of intramolecular disulfide bonds, and amino acid sequence similarity strongly suggest that p400 is the murine ortholog of cubilin. Immunohistochemistry revealed that cubilin (p400) was present in the yolk sac epithelium from day 8 to term. It was also localized in the perforin-positive granules of uNK cells in metrial gland and decidua basalis. Although cubilin is best known as the receptor for intrinsic factor-vitamin B12 in the ileum, it may also act as an endocytic receptor in the kidney and yolk sac where it presumably mediates transcytosis of multiple ligands. The localization of cubilin to uNK cells is the first demonstration of the protein in an immune or non-epithelial cell type. However, the questions of whether cubilin actually interacts with galectin-3 in vivo, and what role cubilin plays, cannot be answered from our results. Because both galectin-3 and cubilin are present in uNK cells, one intriguing hypothesis is that they interact to modulate the immune function of uNK cells, and thus, that they are a part of a mechanism for protecting the fetus from immune rejection.

Description

Keywords

Immunosuppression, Embryo implantation, Placenta, Ovum -- Physiology, Morphogenesis, Ovum implantation, Mice -- Embryology, Immunohistochemistry, Yolk sac, Lectins, Membrane glycoproteins, Cell differentiation, Mice, Protein binding

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