The tetraspanin CD63/lamp3 cycles between endocytic and secretory compartments in human endothelial cells

• Published in: Molecular biology of the cell Vol. 11; no. 5; pp. 1829 - 1843
• Main Authors: Kobayashi, T, Vischer, U M, Rosnoblet, C, Lebrand, C, Lindsay, M, Parton, R G, Kruithof, E K, Gruenberg, J
• Format: Journal Article
• Language: English
• Published: United States The American Society for Cell Biology 01.05.2000
• Subjects: Androstenes - pharmacology; Antibodies, Monoclonal - metabolism; Anticholesteremic Agents - pharmacology; Antigens, CD - immunology; Antigens, CD - metabolism; Cell Compartmentation; Cell Line - drug effects; Endocytosis - physiology; Endothelium, Vascular - cytology; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Humans; Intracellular Membranes - metabolism; Intracellular Membranes - ultrastructure; Kinetics; Organelles - metabolism; P-Selectin - metabolism; Phospholipids - metabolism; Platelet Membrane Glycoproteins - immunology; Platelet Membrane Glycoproteins - metabolism; Tetraspanin 30; Umbilical Veins - cytology; Umbilical Veins - drug effects; Umbilical Veins - metabolism; von Willebrand Factor - immunology; von Willebrand Factor - metabolism
• ISSN: 1059-1524; 1939-4586
• DOI: 10.1091/mbc.11.5.1829

In the present study, we show that in human endothelial cells the tetraspanin CD63/lamp3 distributes predominantly to the internal membranes of multivesicular-multilamellar late endosomes, which contain the unique lipid lysobisphosphatidic acid. Some CD63/lamp3 is also present in Weibel-Palade bodies, the characteristic secretory organelle of these cells. We find that CD63/lamp3 molecules can be transported from late endosomes to Weibel-Palade bodies and thus that CD63/lamp3 cycles between endocytic and biosynthetic compartments; however, movement of CD63/lamp3 is much slower than that of P-selectin, which is known to cycle between plasma membrane and Weibel-Palade bodies. When cells are treated with U18666A, a drug that mimics the Niemann-Pick type C syndrome, both proteins accumulate in late endosomes and fail to reach Weibel-Palade bodies efficiently, suggesting that P-selectin, like CD63/lamp3, cycles via late endosomes. Our data suggest that CD63/lamp3 partitions preferentially within late endosome internal membranes, thus causing its accumulation, and that this mechanism contributes to CD63/lamp3 retention in late endosomes; however, our data also indicate that the protein can eventually escape from these internal membranes and recycle toward Weibel-Palade bodies to be reused. Our observations thus uncover the existence of a selective trafficking route from late endosomes to Weibel-Palade bodies.