Induction of the alternative NF-κB pathway by lymphotoxin αβ (LTαβ) relies on internalization of LTβ receptor.
Details
Serval ID
serval:BIB_9087D22A3CFF
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Induction of the alternative NF-κB pathway by lymphotoxin αβ (LTαβ) relies on internalization of LTβ receptor.
Journal
Molecular and Cellular Biology
ISSN
1098-5549 (Electronic)
ISSN-L
0270-7306
Publication state
Published
Issued date
2011
Volume
31
Number
21
Pages
4319-4334
Language
english
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.
Keywords
Animals, Base Sequence, Biological Transport, Active, Clathrin Heavy Chains/antagonists & inhibitors, Clathrin Heavy Chains/genetics, Cytosol/metabolism, Dynamin II/antagonists & inhibitors, Dynamin II/genetics, HEK293 Cells, HeLa Cells, Humans, Lymphotoxin alpha1, beta2 Heterotrimer/metabolism, Lymphotoxin beta Receptor/chemistry, Lymphotoxin beta Receptor/deficiency, Mice, Mice, Inbred C57BL, Mice, Knockout, Models, Biological, NF-kappa B/metabolism, NF-kappa B p52 Subunit/metabolism, Protein Processing, Post-Translational, Protein-Serine-Threonine Kinases/metabolism, RNA, Small Interfering/genetics, Signal Transduction, TNF Receptor-Associated Factor 3/metabolism, Transcription Factor RelB/deficiency, Transcription Factor RelB/genetics
Pubmed
Web of science
Open Access
Yes
Create date
09/12/2011 10:27
Last modification date
20/08/2019 14:53