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Vol. 18, Issue 8, 3169-3179, August 2007

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Rab11A Controls the Biogenesis of Birbeck Granules by Regulating Langerin Recycling and Stability

Stéphanie Uzan-Gafsou^*, Huguette Bausinger^,,, Fabienne Proamer^,,, Solange Monier^*, Dan Lipsker^,,, Jean-Pierre Cazenave^,,||, Bruno Goud^*, Henri de la Salle^,,, Daniel Hanau^,,, and Jean Salamero^*

*Unité Mixte de Recherche 144 Centre National de la Recherche Scientifique-Institut Curie, Laboratoire "Mécanismes Moléculaires du Transport Intracellulaire," Institut Curie, 75248 Paris Cedex 05, France; U 725 "Biologie des Cellules Dendritiques Humaines" and ^||U 311, Institut National de la Santé et de la Recherche Médicale, F-67065 Strasbourg, France; Université Louis Pasteur, F-67000 Strasbourg, France; and Etablissement Français du Sang-Alsace, F-67065 Strasbourg, France

Submitted September 5, 2006; Revised April 30, 2007; Accepted May 17, 2007
Monitoring Editor: Sandra Schmid

The extent to which Rab GTPases, Rab-interacting proteins, and cargo molecules cooperate in the dynamic organization of membrane architecture remains to be clarified. Langerin, a recycling protein accumulating in the Rab11-positive compartments of Langerhans cells, induces the formation of Birbeck granules (BGs), which are membrane subdomains of the endosomal recycling network. We investigated the role of Rab11A and two members of the Rab11 family of interacting proteins, Rip11 and RCP, in Langerin traffic and the biogenesis of BGs. The overexpression of a dominant-negative Rab11A mutant or Rab11A depletion strongly influenced Langerin traffic and stability and the formation of BGs, whereas modulation of other Rab proteins involved in dynamic regulation of the endocytic-recycling pathway had no effect. Impairment of Rab11A function led to a missorting of Langerin to lysosomal compartments, but inhibition of Langerin degradation by chloroquine did not restore the formation of BGs. Loss of RCP, but not of Rip11, also had a modest, but reproducible effect on Langerin stability and BG biogenesis, pointing to a role for Rab11A–RCP complexes in these events. Our results show that Rab11A and Langerin are required for BG biogenesis, and they illustrate the role played by a Rab GTPase in the formation of a specialized subcompartment within the endocytic-recycling system.

The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

Address correspondence to: Jean Salamero (jean.salamero{at}curie.fr) or Daniel Hanau (daniel.hanau{at}efs-alsace.fr).

Abbreviations used: BG, Birbeck granule; ERC, endosomal recycling compartment; LC, Langerhans cell; siRNA, small interfering RNA; TfR, transferrin receptor.