Palmitoylation of NOD1 and NOD2 is required for bacterial sensing

NODs require S-palmitoylation to signal The compartmentalization of proteins within the cell is essential for their function. The addition of lipid molecules redistributes proteins to the cell surface or to membrane-bound organelles. Working in transgenic mice and in tissue cultured cells, Lu et al. found that nucleotide oligomerization domain–like receptors 1 and 2 (NOD1 and NOD2), two proteins responsible for detecting bacterial products, required lipid modifications for their recruitment to the cell membrane and function. The specific modification, palmitoylation at a cysteine thiol, was mediated by the enzyme ZDHHC5. Loss of ZDHHC5 or removal of key modification residues in NOD1 and NOD2 abolished their function, compromising antibacterial responses. Human variants of NOD2 display altered palmitoylation, which could help to explain many inflammatory conditions, such as irritable bowel syndrome. Science , this issue p. 460