title: The tetraspanin CD63/lamp3 cycles between endocytic and secretory compartments in human endothelial cells.
abstract: 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.
authors.affiliation: Department of Biochemistry, Sciences II, University of Geneva, 1211-Geneva-4, Switzerland.
authors.forename: T
authors.initials: T
authors.lastname: Kobayashi
authors.forename: U M
authors.initials: UM
authors.lastname: Vischer
authors.forename: C
authors.initials: C
authors.lastname: Rosnoblet
authors.forename: C
authors.initials: C
authors.lastname: Lebrand
authors.forename: M
authors.initials: M
authors.lastname: Lindsay
authors.forename: R G
authors.initials: RG
authors.lastname: Parton
authors.forename: E K
authors.initials: EK
authors.lastname: Kruithof
authors.forename: J
authors.initials: J
authors.lastname: Gruenberg
mesh_terms: D000736:Androstenes / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000378:metabolism; D000924:Anticholesteremic Agents / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D002451:Cell Compartmentation; D002460:Cell Line / Q000187:drug effects; D004705:Endocytosis / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism / Q000648:ultrastructure; D007700:Kinetics; D015388:Organelles / Q000378:metabolism; D019007:P-Selectin / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D060149:Tetraspanin 30; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014841:von Willebrand Factor / Q000276:immunology / Q000378:metabolism
chemical_list: D000736:Androstenes; D000911:Antibodies, Monoclonal; D000924:Anticholesteremic Agents; D015703:Antigens, CD; C554586:CD63 protein, human; D019007:P-Selectin; D010743:Phospholipids; D010980:Platelet Membrane Glycoproteins; D060149:Tetraspanin 30; D014841:von Willebrand Factor; C006261:3-beta-(2-(diethylamino)ethoxy)androst-5-en-17-one