Birbeck Granules Are Subdomains of Endosomal Recycling Compartment in Human Epidermal Langerhans Cells, Which Form Where Langerin Accumulates

摘要

Birbeck granules are unusual rod-shaped structures specific toepidermal Langerhans cells, whose origin and function remainundetermined. We investigated the intracellular location and fate ofLangerin, a protein implicated in Birbeck granule biogenesis, inhuman epidermal Langerhans cells. In the steady state, Langerin ispredominantly found in the endosomal recycling compartment and inBirbeck granules. Langerin internalizes by classical receptor-mediatedendocytosis and the first Birbeck granules accessible to endocytosedLangerin are those connected to recycling endosomes in thepericentriolar area, where Langerin accumulates. Drug-inducedinhibition of endocytosis results in the appearance of abundantopen-ended Birbeck granule-like structures appended to the plasmamembrane, whereas inhibition of recycling induces Birbeck granules tomerge with a tubular endosomal network. In mature Langerhans cells,Langerin traffic is abolished and the loss of internal Langerin isassociated with a concomitant depletion of Birbeck granules. Ourresults demonstrate an exchange of Langerin between early endosomalcompartments and the plasma membrane, with dynamic retention in theendosomal recycling compartment. They show that Birbeck granules arenot endocytotic structures, rather they are subdomains of the endosomalrecycling compartment that form where Langerin accumulates. Finally,our results implicate ADP-ribosylation factor proteins in Langerintrafficking and the exchange between Birbeck granules and otherendosomal membranes.