title: Birbeck granules are subdomains of endosomal recycling compartment in human epidermal Langerhans cells, which form where Langerin accumulates.
abstract: Birbeck granules are unusual rod-shaped structures specific to epidermal Langerhans cells, whose origin and function remain undetermined. We investigated the intracellular location and fate of Langerin, a protein implicated in Birbeck granule biogenesis, in human epidermal Langerhans cells. In the steady state, Langerin is predominantly found in the endosomal recycling compartment and in Birbeck granules. Langerin internalizes by classical receptor-mediated endocytosis and the first Birbeck granules accessible to endocytosed Langerin are those connected to recycling endosomes in the pericentriolar area, where Langerin accumulates. Drug-induced inhibition of endocytosis results in the appearance of abundant open-ended Birbeck granule-like structures appended to the plasma membrane, whereas inhibition of recycling induces Birbeck granules to merge with a tubular endosomal network. In mature Langerhans cells, Langerin traffic is abolished and the loss of internal Langerin is associated with a concomitant depletion of Birbeck granules. Our results demonstrate an exchange of Langerin between early endosomal compartments and the plasma membrane, with dynamic retention in the endosomal recycling compartment. They show that Birbeck granules are not endocytotic structures, rather they are subdomains of the endosomal recycling compartment that form where Langerin accumulates. Finally, our results implicate ADP-ribosylation factor proteins in Langerin trafficking and the exchange between Birbeck granules and other endosomal membranes.
authors.affiliation: Unité Mixte de Recherche 144 Centre National de la Recherche Scientifique, Laboratoire Mécanismes Moléculaires du Transport Intracellulaire, Institut Curie, 75248 Paris, France.
authors.forename: Ray
authors.initials: R
authors.lastname: Mc Dermott
authors.forename: Umit
authors.initials: U
authors.lastname: Ziylan
authors.forename: Danièle
authors.initials: D
authors.lastname: Spehner
authors.forename: Huguette
authors.initials: H
authors.lastname: Bausinger
authors.forename: Dan
authors.initials: D
authors.lastname: Lipsker
authors.forename: Mieke
authors.initials: M
authors.lastname: Mommaas
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Cazenave
authors.forename: Graça
authors.initials: G
authors.lastname: Raposo
authors.forename: Bruno
authors.initials: B
authors.lastname: Goud
authors.forename: Henri
authors.initials: H
authors.lastname: de la Salle
authors.forename: Jean
authors.initials: J
authors.lastname: Salamero
authors.forename: Daniel
authors.initials: D
authors.lastname: Hanau
mesh_terms: D015703:Antigens, CD; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D020126:Brefeldin A / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002451:Cell Compartmentation; D002462:Cell Membrane / Q000648:ultrastructure; D002478:Cells, Cultured; D002502:Centrioles / Q000648:ultrastructure; D015638:Cytochalasin D / Q000494:pharmacology; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D004705:Endocytosis; D011992:Endosomes / Q000737:chemistry* / Q000378:metabolism*; D000078404:Epidermal Cells; D005455:Fluorescent Antibody Technique; D006801:Humans; D007700:Kinetics; D007801:Langerhans Cells / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D018613:Microscopy, Confocal; D016253:Microscopy, Immunoelectron; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines
chemical_list: D015703:Antigens, CD; D000954:Antigens, Surface; D019086:Bridged Bicyclo Compounds, Heterocyclic; C121916:CD207 protein, human; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D011500:Protein Synthesis Inhibitors; D011993:Recombinant Fusion Proteins; D013844:Thiazoles; D053778:Thiazolidines; D020126:Brefeldin A; D015638:Cytochalasin D; C037067:latrunculin A