Induction of the Alternative NF-kappa B Pathway by Lymphotoxin alpha beta (LT alpha beta) Relies on Internalization of LT beta Receptor

C Ganeff, C Remouchamps, L Boutaffala, Cecile Benezech, G Galopin, S Vandepaer, F Bouillenne, S Ormenese, A Chariot, P Schneider, Jorge Caamano, J Piette, E Dejardin

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37 Citations (Scopus)

Abstract

Several tumor necrosis factor receptor (TNFR) family members activate both the classical and the alternative NF-kappa B pathways. However, how a single receptor engages these two distinct pathways is still poorly understood. Using lymphotoxin beta receptor (LT beta R) as a prototype, we showed that activation of the alternative, but not the classical, NF-kappa B pathway relied on internalization of the receptor. Further molecular analyses revealed a specific cytosolic region of LT beta R essential for its internalization, TRAF3 recruitment, and p100 processing. Interestingly, we found that dynamin-dependent, but clathrin-independent, internalization of LT beta R appeared to be required for the activation of the alternative, but not the classical, NF-kappa B pathway. In vivo, ligand-induced internalization of LT beta R in mesenteric lymph node stromal cells correlated with induction of alternative NF-kappa B target genes. Thus, our data shed light on LT beta R cellular trafficking as a process required for specific biological functions of NF-kappa B.
Original languageEnglish
Pages (from-to)4319-4334
Number of pages16
JournalMolecular and Cellular Biology
Volume31
Issue number21
DOIs
Publication statusPublished - 1 Nov 2011

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