Palmitoylation of NOD1 and NOD2 is required for bacterial sensing

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

doi:10.1126/science.aau6391

Palmitoylation of NOD1 and NOD2 is required for bacterial sensing

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

Research output: Contribution to journal › Article › peer-review

152 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	460-467
Number of pages	8
Journal	Science
Volume	366
Issue number	6464
DOIs	https://doi.org/10.1126/science.aau6391
Publication status	Published - Oct 25 2019
Externally published	Yes

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© 2019 American Association for the Advancement of Science. All rights reserved.

ASJC Scopus Subject Areas

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Lu, Y, Zheng, Y, Coyaud, É, Zhang, C, Selvabaskaran, A, Yu, Y, Xu, Z, Weng, X, Chen, JS, Meng, Y, Warner, N, Cheng, X, Liu, Y, Yao, B, Hu, H, Xia, Z, Muise, AM, Klip, A, Brumell, JH, Girardin, SE, Ying, S, Fairn, GD, Raught, B, Sun, Q & Neculai, D 2019, 'Palmitoylation of NOD1 and NOD2 is required for bacterial sensing', Science, vol. 366, no. 6464, pp. 460-467. https://doi.org/10.1126/science.aau6391

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title = "Palmitoylation of NOD1 and NOD2 is required for bacterial sensing",

abstract = "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.",

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

year = "2019",

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doi = "10.1126/science.aau6391",

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T1 - Palmitoylation of NOD1 and NOD2 is required for bacterial sensing

AU - Lu, Yan

AU - Zheng, Yuping

AU - Coyaud, Étienne

AU - Zhang, Chao

AU - Selvabaskaran, Apiraam

AU - Yu, Yuyun

AU - Xu, Zizhen

AU - Weng, Xialian

AU - Chen, Ji Shun

AU - Meng, Ying

AU - Warner, Neil

AU - Cheng, Xiawei

AU - Liu, Yangyang

AU - Yao, Bingpeng

AU - Hu, Hu

AU - Xia, Zonping

AU - Muise, Aleixo M.

AU - Klip, Amira

AU - Brumell, John H.

AU - Girardin, Stephen E.

AU - Ying, Songmin

AU - Fairn, Gregory D.

AU - Raught, Brian

AU - Sun, Qiming

AU - Neculai, Dante

PY - 2019/10/25

Y1 - 2019/10/25

N2 - 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.

AB - 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.

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Palmitoylation of NOD1 and NOD2 is required for bacterial sensing

Abstract

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