NOD proteins: an intracellular pathogen-recognition system or signal transduction modifiers?

NOD1 and NOD2 are members of a diverse family of cytoplasmic proteins that contain C-terminal leucine-rich repeats. Because of their similarity to a family of plant proteins involved in pathogen resistance, and because mutations in Card15, encoding NOD2, are frequently found in familial cases of Crohn's disease--an intestinal malady of excessive inflammation--NOD proteins have been proposed to fulfill a role in the intracellular sensing of bacteria. Indeed, NOD proteins seem to alter the ability of cells to respond to fragments from bacterial cell walls. This system could function analogously to the Toll-like receptors--extracellular proteins that play an essential role in pathogen recognition. However, the idea of an intracellular system that specifically recognizes bacterial cell components is controversial and alternative functions of NODs are possible including regulating signal transduction systems.