TY - JOUR
T1 - Membrane recruitment of NOD2 in intestinal epithelial cells is essential for nuclear factor-ΚB activation in muramyl dipeptide recognition
AU - Barnich, Nicolas
AU - Aguirre, Jose E.
AU - Reinecker, Hans Christian
AU - Xavier, Ramnik
AU - Podolsky, Daniel K.
PY - 2005/7
Y1 - 2005/7
N2 - Nucleotide oligomerization domain (NOD) 2 functions as a mammalian cytosolic pathogen recognition molecule, and mutant forms have been genetically linked to Crohn's disease (CD). NOD2 associates with the caspase activation and recruitment domain of RIP-like interacting caspase-like apoptosis regulatory protein kinase (RICK)/RIP2 and activates nuclear factor (NF)-ΚB in epithelial cells and macrophages, whereas NOD2 mutant 3020insC, which is associated with CD, shows an impaired ability to activate NF-ΚB. To gain insight into the molecular mechanisms of NOD2 function, we performed a functional analysis of deletion and substitution NOD2 mutants. NOD2, but not NOD2 3020insC mutant, associated with cell surface membranes of intestinal epithelial cells. Membrane targeting and subsequent NF-ΚB activation are mediated by two leucine residues and a tryptophan-containing motif in the COOH-terminal domain of NOD2. The membrane targeting of NOD2 is required for NF-ΚB activation after the recognition of bacterial muramyl dipeptide in intestinal epithelial cells.
AB - Nucleotide oligomerization domain (NOD) 2 functions as a mammalian cytosolic pathogen recognition molecule, and mutant forms have been genetically linked to Crohn's disease (CD). NOD2 associates with the caspase activation and recruitment domain of RIP-like interacting caspase-like apoptosis regulatory protein kinase (RICK)/RIP2 and activates nuclear factor (NF)-ΚB in epithelial cells and macrophages, whereas NOD2 mutant 3020insC, which is associated with CD, shows an impaired ability to activate NF-ΚB. To gain insight into the molecular mechanisms of NOD2 function, we performed a functional analysis of deletion and substitution NOD2 mutants. NOD2, but not NOD2 3020insC mutant, associated with cell surface membranes of intestinal epithelial cells. Membrane targeting and subsequent NF-ΚB activation are mediated by two leucine residues and a tryptophan-containing motif in the COOH-terminal domain of NOD2. The membrane targeting of NOD2 is required for NF-ΚB activation after the recognition of bacterial muramyl dipeptide in intestinal epithelial cells.
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U2 - 10.1083/jcb.200502153
DO - 10.1083/jcb.200502153
M3 - Article
C2 - 15998797
AN - SCOPUS:22244465576
SN - 0021-9525
VL - 170
SP - 21
EP - 26
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 1
ER -