Induction of the alternative NF-κB pathway by lymphotoxin αβ (LTαβ) relies on internalization of LTβ receptor

Corinne Ganeff, Caroline Remouchamps, Layla Boutaffala, Cécile Benezech, Géraldine Galopin, Sarah Vandepaer, Fabrice Bouillenne, Sandra Ormenese, Alain Chariot, Pascal Schneider, Jorge Caamaño, Jacques Piette, Emmanuel Dejardin

Research output: Contribution to journalArticlepeer-review

Abstract

Several tumor necrosis factor receptor (TNFR) family members activate both the classical and the alternative NF-κB pathways. However, how a single receptor engages these two distinct pathways is still poorly understood. Using lymphotoxin β receptor (LTβR) as a prototype, we showed that activation of the alternative, but not the classical, NF-κB pathway relied on internalization of the receptor. Further molecular analyses revealed a specific cytosolic region of LTβR essential for its internalization, TRAF3 recruitment, and p100 processing. Interestingly, we found that dynamin-dependent, but clathrin-independent, internalization of LTβR appeared to be required for the activation of the alternative, but not the classical, NF-κB pathway. In vivo, ligand-induced internalization of LTβR in mesenteric lymph node stromal cells correlated with induction of alternative NF-κB target genes. Thus, our data shed light on LTβR cellular trafficking as a process required for specific biological functions of NF-κB.
Original languageEnglish
Pages (from-to)4319-34
Number of pages16
JournalMolecular and Cellular Biology
Volume31
Issue number21
DOIs
Publication statusPublished - Nov 2011

Keywords

  • Animals
  • Base Sequence
  • Biological Transport, Active
  • Clathrin Heavy Chains
  • Cytosol
  • Dynamin II
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Lymphotoxin alpha1, beta2 Heterotrimer
  • Lymphotoxin beta Receptor
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Biological
  • NF-kappa B
  • NF-kappa B p52 Subunit
  • Protein Processing, Post-Translational
  • Protein-Serine-Threonine Kinases
  • RNA, Small Interfering
  • Signal Transduction
  • TNF Receptor-Associated Factor 3
  • Transcription Factor RelB

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