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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 language | English |
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Pages (from-to) | 4319-4334 |
Number of pages | 16 |
Journal | Molecular and Cellular Biology |
Volume | 31 |
Issue number | 21 |
DOIs | |
Publication status | Published - 1 Nov 2011 |
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Dive into the research topics of 'Induction of the Alternative NF-kappa B Pathway by Lymphotoxin alpha beta (LT alpha beta) Relies on Internalization of LT beta Receptor'. Together they form a unique fingerprint.Projects
- 1 Finished
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NF-kB/ReIB Function during Lymph Node Development
Biotechnology & Biological Sciences Research Council
1/10/06 → 31/05/10
Project: Research Councils