NLRC4 (D5Y8E) Rabbit mAb

The nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family of proteins is a diverse family of cytoplasmic innate immune receptors. They are characterized by the presence of an amino-terminal effector domain, which is often either a caspase activation and recruitment domain (CARD) or a pyrin domain (PYD), followed by a NACHT domain and carboxy-terminal leucine-rich-repeats (LRR) involved in recognition of pathogen-associated molecular patterns (PAMPs) (1). NLR proteins play a variety of roles during the innate immune response including pathogen sensing, transcriptional activation of proinflammatory cytokines through NF-κB, transcriptional activation of type I interferons through IRFs, and formation of inflammasomes leading to activation of inflammatory caspases (1-7).The NLRC4 (IPAF) inflammasome forms in response to bacterial flagellin as well as components of the bacterial conserved type II secretion system (TTSS) (8-12). Ligand detection and ligand-dependent NLRC4 oligomerization and inflammasome activation require the NAIP family of proteins (13,14). In mice, NAIP5 and NAIP6 associate with flagellin, while NAIP2 interacts with TTSS rod proteins (13,14). In humans, NAIP recognizes the TTSS needle protein Cprl (14). In addition, NLRC4 is phosphorylated by PKCδ in response to bacterial infection and this phosphorylation is required for inflammasome assembly and caspase-1 activation (15). 1.Elinav, E. et al. (2011) Immunity 34, 665-79. 2.Inohara, N. et al. (1999) J Biol Chem 274, 14560-7. 3.Ogura, Y. et al. (2001) J Biol Chem 276, 4812-8. 4.Sabbah, A. et al. (2009) Nat Immunol 10, 1073-80. 5.Mariathasan, S. et al. (2004) Nature 430, 213-8. 6.Agostini, L. et al. (2004) Immunity 20, 319-25. 7.Martinon, F. et al. (2002) Mol Cell 10, 417-26. 8.Poyet, J.L. et al. (2001) J Biol Chem 276, 28309-13. 9.Mariathasan, S. et al. (2004) Nature 430, 213-8. 10.Franchi, L. et al. (2006) Nat Immunol 7, 576-82. 11.Miao, E.A. et al. (2006) Nat Immunol 7, 569-75. 12.Miao, E.A. et al. (2010) Proc Natl Acad Sci U S A 107, 3076-80. 13.Kofoed, E.M. and Vance, R.E. (2011) Nature 477, 592-5. 14.Zhao, Y. et al. (2011) Nature 477, 596-600. 15.Qu, Y. et al. (2012) Nature 490, 539-42.