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

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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 2005

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Acetylmuramyl-Alanyl-Isoglutamine
Epithelial Cells
Crohn Disease
Membranes
Apoptosis Regulatory Proteins
Caspases
Leucine
Tryptophan
Protein Kinases
Nucleotides
Macrophages
Cell Membrane

ASJC Scopus subject areas

  • Cell Biology

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Membrane recruitment of NOD2 in intestinal epithelial cells is essential for nuclear factor-ΚB activation in muramyl dipeptide recognition. / Barnich, Nicolas; Aguirre, Jose E.; Reinecker, Hans Christian; Xavier, Ramnik; Podolsky, Daniel K.

In: Journal of Cell Biology, Vol. 170, No. 1, 07.2005, p. 21-26.

Research output: Contribution to journalArticle

Barnich, Nicolas ; Aguirre, Jose E. ; Reinecker, Hans Christian ; Xavier, Ramnik ; Podolsky, Daniel K. / Membrane recruitment of NOD2 in intestinal epithelial cells is essential for nuclear factor-ΚB activation in muramyl dipeptide recognition. In: Journal of Cell Biology. 2005 ; Vol. 170, No. 1. pp. 21-26.
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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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