title: Induction of the alternative NF-κB pathway by lymphotoxin αβ (LTαβ) relies on internalization of LTβ receptor.
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.
authors: Unit of Molecular Immunology and Signal Transduction, GIGA-Research, University of Liège, Avenue de l'Hôpital 1, Sart-Tilman, CHU, B34, 4000 Liège, Belgium.
authors: Corinne
authors: C
authors: Ganeff
authors: Caroline
authors: C
authors: Remouchamps
authors: Layla
authors: L
authors: Boutaffala
authors: Cécile
authors: C
authors: Benezech
authors: Géraldine
authors: G
authors: Galopin
authors: Sarah
authors: S
authors: Vandepaer
authors: Fabrice
authors: F
authors: Bouillenne
authors: Sandra
authors: S
authors: Ormenese
authors: Alain
authors: A
authors: Chariot
authors: Pascal
authors: P
authors: Schneider
authors: Jorge
authors: J
authors: Caamaño
authors: Jacques
authors: J
authors: Piette
authors: Emmanuel
authors: E
authors: Dejardin
mesh_terms: D000818:Animals; D001483:Base Sequence; D001693:Biological Transport, Active; D033922:Clathrin Heavy Chains / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D034285:Dynamin II / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D053361:Lymphotoxin alpha1, beta2 Heterotrimer / Q000378:metabolism*; D053259:Lymphotoxin beta Receptor / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism*; D052003:NF-kappa B p52 Subunit / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D048008:TNF Receptor-Associated Factor 3 / Q000378:metabolism; D051841:Transcription Factor RelB / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D000097782:NF-kappaB-Inducing Kinase
chemical_list: D033922:Clathrin Heavy Chains; D034285:Dynamin II; D053361:Lymphotoxin alpha1, beta2 Heterotrimer; D053259:Lymphotoxin beta Receptor; D016328:NF-kappa B; D052003:NF-kappa B p52 Subunit; D017346:Protein Serine-Threonine Kinases; D034741:RNA, Small Interfering; D048008:TNF Receptor-Associated Factor 3; D051841:Transcription Factor RelB; D000097782:NF-kappaB-Inducing Kinase; C497594:Relb protein, mouse