Membrane recruitment of NOD2 in intestinal epithelial cells is essential for nuclear factor-ΚB activation in muramyl dipeptide recognition

Nicolas Barnich, Jose E. Aguirre, Hans Christian Reinecker, Ramnik Xavier, Daniel K. Podolsky

Research output: Contribution to journalArticle

206 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)21-26
Number of pages6
JournalJournal of Cell Biology
Volume170
Issue number1
DOIs
StatePublished - Jul 1 2005

ASJC Scopus subject areas

  • Cell Biology

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