Journal Article

Palmitoylation of NOD1 and NOD2 is required for bacterial sensing

Fairn, Gregory D., Coyaud, Étienne, Chen, Ji Shun, Muise, Aleixo M., Selvabaskaran, Apiraam, Yao, Bingpeng, Raught, Brian, Yu, Yuyun, Brumell, John H., Liu, Yangyang, Sun, Qiming, Xu, Zizhen, Girardin, Stephen E., Hu, Hu, Weng, Xialian, Ying, Songmin, Meng, Ying, Lu, Yan, Zhang, Chao, Klip, Amira, Cheng, Xiawei, Warner, Neil, Zheng, Yuping, Xia, Zonping, Neculai, Dante

2019

Overview

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.

• Publisher: American Association for the Advancement of Science,The American Association for the Advancement of Science
• Subject: Acyltransferases - metabolism / Animals / Bacteria / Cell membranes / Cell surface / Cysteine - chemistry / Endosomes / HCT116 Cells / HEK293 Cells / Human behavior / Humans / Immune response / Immune system / Inflammatory bowel diseases / Intestine / Intracellular / Intracellular signalling / Irritable bowel syndrome / Lipids / Lipoylation / Localization / Macrophages - immunology / Macrophages - microbiology / Membranes / Mice / Mice, Inbred C57BL / Mice, Knockout / Microorganisms / Mutation / Nod1 protein / Nod1 Signaling Adaptor Protein - chemistry / NOD2 protein / Nod2 Signaling Adaptor Protein - chemistry / Nucleotides / Oligomerization / Organelles / Palmitoylation / Palmitoyltransferase / Pattern recognition / Peptidoglycan / Peptidoglycans / Phagosomes - immunology / Phagosomes - microbiology / Protein Processing, Post-Translational / Proteins / RAW 264.7 Cells / Receptors / Recruitment / Salmonella typhimurium / Signal Transduction / Signaling / Transgenic mice