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Vol. 13, Issue 1, 317-335, January 2002
#
Unité Mixte de Recherche 144 Centre National de la
Recherche Scientifique-Institut Curie, *Laboratoire Mécanismes
Moléculaires du Transport Intracellulaire and
¶Laboratoire de Microscopie Electronique, Institut Curie,
75248 Paris, France; 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.
Institut National de la Santé
et de la Recherche Médicale EP 99-08 Biologie des Cellules
Dendritiques Humaines and Institut National de la
Santé et de la Recherche Médicale U 311, Etablissement
Français du Sang-Alsace, 67065 Strasbourg, France; and
§Department of Dermatology and Center for Electron
Microscopy, Leidem University Medical Center, 2300 RA Leiden, The
Netherlands
These authors contributed equally to this work and
are listed in alphabetical order.
#
Corresponding author. E-mail address:
daniel.hanau{at}efs-alsace.fr.
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