title: Divergent fates of P- and E-selectins after their expression on the plasma membrane.
abstract: P-selectin and E-selectin are related adhesion receptors for monocytes and neutrophils that are expressed by stimulated endothelial cells. P-selectin is stored in Weibel-Palade bodies, and it reaches the plasma membrane after exocytosis of these granules. E-selectin is not stored, and its synthesis is induced by cytokines. We studied the fate of the two proteins after their surface expression by following the intracellular routing of internalized antibodies to the selectins. By immunofluorescent staining, P-selectin antibody was first seen in endosomes, then in the Golgi region, and finally in Weibel-Palade bodies. In contrast, the E-selectin antibody was detected only in endosomes and lysosomes. Subcellular fractionation of cells after 4 h chase confirmed the localization of P-selectin antibody in storage granules and of the E-selectin antibody in lysosomes. In AtT-20 cells, a mouse pituitary cell line, transfected with P- or E-selectin, only P-selectin was delivered to the endogenous adrenocorticotrophic hormone storage granules after endocytosis. Deletion of the cytoplasmic domain abolished internalization. In summary, after a brief surface exposure, internalized E-selectin is degraded in the lysosomes, whereas P-selectin returns to the storage granules from where it can be reused.
authors.affiliation: Department of Medicine, New England Medical Center, Boston, Massachusetts.
authors.forename: M
authors.initials: M
authors.lastname: Subramaniam
authors.forename: J A
authors.initials: JA
authors.lastname: Koedam
authors.forename: D D
authors.initials: DD
authors.lastname: Wagner
mesh_terms: D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002458:Cell Fractionation; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D006224:Cricetinae; D004247:DNA; D019040:E-Selectin; D004705:Endocytosis; D005455:Fluorescent Antibody Technique; D006801:Humans; D051379:Mice; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D014162:Transfection
chemical_list: D015815:Cell Adhesion Molecules; D019040:E-Selectin; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D004247:DNA