Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.11.1.7 (peroxidase)
 65,474 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The apical domain of epithelial cells lining the proximal tubule and the yolk sac is characterized by the development of extensive microvilli which limit intermicrovillar spaces backed on their cytoplasmic aspect by a coat of clathrin. These membrane areas which give rise to endocytic vesicles are characterized by the expression on their outer aspect of two high molecular weight glycoproteins: gp330 and gp280. In this study we report on an epithelial cell line, BN/MSV, derived from a yolk sac carcinoma which expresses these two glycoproteins. By indirect immunofluorescence, gp330 and gp280 were detectable on the cell surface and after permeabilization in intracytoplasmic vesicles. At the ultrastructural level they were concentrated in clathrin-coated membrane areas and although gp280 could also be detected in non-coated areas. The two proteins were synthesized independently in the form of high molecular weight polymers by biosynthetically labeled BN/MSV cells. Both were released in the supernatant, but, in spite of previously reported similarities by peptide mapping, only gp330 coprecipitated with a 45 kDa protein comigrating with the alpha 2-macroglobulin receptor-associated protein (MRAP). Culture of the cells in the presence of antibodies to gp280 and to a lesser extent of antibodies to gp330 inhibited the internalization of [14C]sucrose and peroxidase. When followed intracellularly at the ultrastructural level, the compartments containing peroxidase in the presence of anti-gp280 or gp330 antibodies were morphologically distinct from those observed under control conditions: vesicles were of smaller size and irregular shape and accumulation in lysosomes was delayed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunofunctional properties of a yolk sac epithelial cell line expressing two proteins gp280 and gp330 of the intermicrovillar area of proximal tubule cells: inhibition of endocytosis by the specific antibodies. 766 54

Previous studies have identified two high-molecular weight (280 and 330 kd) glycoproteins expressed by coated pits of the proximal renal tubule and yolk sac and have further established that, in vivo, antibodies to gp280 but not to gp330 induce fetal malformations. In the present study, we report the effect of these antibodies on the endocytic process by yolk sac visceral epithelial cells of rat embryos explanted at day 10 of gestation. Antibodies to gp280 markedly altered development of the yolk sac and embryo, induced malformations, inhibited by 40% the uptake of [14C] sucrose and perturbed the intracellular traffic of internalized proteins. Under control conditions, rat immunoglobulin G present in the culture medium was immunolocalized in lysosomes of epithelial cells, whereas in the presence of antibody, it was detected in small vesicles scattered through the apical cytoplasm. Alterations of the endocytic pathway were confirmed by experiments analyzing the uptake of peroxidase added to the medium for 2 to 60 minutes. The initial compartments of endocytosis visualized by peroxidase were increased in size and abnormal in shape and the transfer of the internalized peroxidase to the lysosomal compartment was delayed. In contrast, antibodies to gp330 had a minimal effect on embryonic development and did not induce fetal malformations. Endocytosis was only modestly altered; uptake of [14C] sucrose was decreased by 25%, and only minor modifications of the intracellular transit of peroxidase could be detected. We suggest that the key role of anti-gp280 antibodies is via trapping of the target antigen in the early endocytic compartment thus preventing its normal function in lysosomal transfer.
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PMID:Antibodies to the 280-kd coated pit protein, target of teratogenic antibodies, produce alterations in the traffic of internalized proteins. 799 55