Palmitoylation of NOD1 and NOD2 is required for bacterial sensing-Reference-Cited by-同舟云学术

Palmitoylation of NOD1 and NOD2 is required for bacterial sensing

Published:2019-10-25 Issue:6464 Volume:366 Page:460-467
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Lu Yan¹²^ORCID,Zheng Yuping¹^ORCID,Coyaud Étienne³^ORCID,Zhang Chao⁴⁵,Selvabaskaran Apiraam⁶^ORCID,Yu Yuyun¹,Xu Zizhen¹^ORCID,Weng Xialian¹,Chen Ji Shun¹^ORCID,Meng Ying¹,Warner Neil⁷^ORCID,Cheng Xiawei⁸,Liu Yangyang⁹^ORCID,Yao Bingpeng¹⁰^ORCID,Hu Hu⁹^ORCID,Xia Zonping¹¹^ORCID,Muise Aleixo M.⁷^ORCID,Klip Amira¹²^ORCID,Brumell John H.⁷¹³,Girardin Stephen E.⁶^ORCID,Ying Songmin¹⁰,Fairn Gregory D.²^ORCID,Raught Brian³¹⁴^ORCID,Sun Qiming⁸^ORCID,Neculai Dante¹^ORCID

Affiliation:

1. Department of Cell Biology, and Department of Pathology Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

2. Keenan Research Centre for Biomedical Sciences, St. Michael’s Hospital, Toronto, ON, Canada.

3. Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.

4. Department of Anatomy, School of Medicine, Zhejiang University, China School of Medicine, Zhejiang University, Hangzhou 310058, China.

5. Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.

6. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.

7. SickKids Inflammatory Bowel Disease Center and Cell Biology Program, Research Institute, Hospital for Sick Children, Toronto, ON, Canada.

8. Department of Biochemistry, and Department of Cardiology of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China.

9. Department of Pathology, School of Medicine, Zhejiang University, Hangzhou 310058, China.

10. Department of Pharmacology and Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Institute of Respiratory Diseases, Zhejiang University School of Medicine, Hangzhou 310009, China.

11. Translational Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.

12. Cell Biology Program, Research Institute, The Hospital for Sick Children, Peter Gilgan Centre for Research and Learning (PGCRL), Toronto, ON, Canada.

13. Department of Molecular Genetics and Institute of Medical Science, University of Toronto, Toronto, ON, Canada.

14. Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.

Abstract

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

Funder

Canadian Institutes of Health Research

National Natural Science Foundation of China

Key Program of Zhejiang Provincial Natural Science Foundation of China

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference47 articles.

1. NOD proteins: regulators of inflammation in health and disease

2. NOD1 and NOD2: Signaling, Host Defense, and Inflammatory Disease

3. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease