NOD2-C2 - a novel NOD2 isoform activating NF-κB in a muramyl dipeptide-independent manner
- Equal contributors
1 Genome Analysis, Leibniz Institute for Age Research - Fritz Lipmann Institute, Beutenbergstrasse 11, 07745 Jena, Germany
2 Membrane Trafficking, Leibniz Institute for Age Research - Fritz Lipmann Institute, Beutenbergstrasse 11, 07745 Jena, Germany
3 Institute of Clinical Molecular Biology, University Hospital Schleswig-Holstein, Christian Albrechts University, Schittenhelmstrasse 12, 24105 Kiel, Germany
BMC Research Notes 2010, 3:224 doi:10.1186/1756-0500-3-224Published: 10 August 2010
The innate immune system employs several receptor families that form the basis of sensing pathogen-associated molecular patterns. NOD (nucleotide-binding and oligomerization domain) like receptors (NLRs) comprise a group of cytosolic proteins that trigger protective responses upon recognition of intracellular danger signals. NOD2 displays a tandem caspase recruitment domain (CARD) architecture, which is unique within the NLR family.
Here, we report a novel alternative transcript of the NOD2 gene, which codes for a truncated tandem CARD only protein, called NOD2-C2. The transcript isoform is highest expressed in leucocytes, a natural barrier against pathogen invasion, and is strictly linked to promoter usage as well as predominantly to one allele of the single nucleotide polymorphism rs2067085. Contrary to a previously identified truncated single CARD NOD2 isoform, NOD2-S, NOD2-C2 is able to activate NF-κB in a dose dependent manner independently of muramyl dipeptide (MDP). On the other hand NOD2-C2 competes with MDPs ability to activate the NOD2-driven NF-κB signaling cascade.
NOD2 transcripts having included an alternative exon downstream of exon 3 (exon 3a) are the endogenous equivalents of a previously described in vitro construct with the putative protein composed of only the two N-terminal CARDs. This protein form (NOD2-C2) activates NF-κB independent of an MDP stimulus and is a potential regulator of NOD2 signaling.