First Author | Lu Y | Year | 2019 |
Journal | Science | Volume | 366 |
Issue | 6464 | Pages | 460-467 |
PubMed ID | 31649195 | Mgi Jnum | J:287065 |
Mgi Id | MGI:6414746 | Doi | 10.1126/science.aau6391 |
Citation | Lu Y, et al. (2019) Palmitoylation of NOD1 and NOD2 is required for bacterial sensing. Science 366(6464):460-467 |
abstractText | The nucleotide oligomerization domain (NOD)-like receptors 1 and 2 (NOD1/2) are intracellular pattern-recognition proteins that activate immune signaling pathways in response to peptidoglycans associated with microorganisms. Recruitment to bacteria-containing endosomes and other intracellular membranes is required for NOD1/2 signaling, and NOD1/2 mutations that disrupt membrane localization are associated with inflammatory bowel disease and other inflammatory conditions. However, little is known about this recruitment process. We found that NOD1/2 S-palmitoylation is required for membrane recruitment and immune signaling. ZDHHC5 was identified as the palmitoyltransferase responsible for this critical posttranslational modification, and several disease-associated mutations in NOD2 were found to be associated with defective S-palmitoylation. Thus, ZDHHC5-mediated S-palmitoylation of NOD1/2 is critical for their ability to respond to peptidoglycans and to mount an effective immune response. |