A Golgi-resident GPR108 cooperates with E3 ubiquitin ligase Smurf1 to suppress antiviral innate immunity

Mengyuan Zhao; Yong Zhang; Lihua Qiang; Zhe Lu; Zhuo Zhao; Yesheng Fu; Bo Wu; Qiyao Chai; Pupu Ge; Zehui Lei; Xinwen Zhang; Bingxi Li; Jing Wang; Lingqiang Zhang; Cui Hua Liu

doi:10.1016/j.celrep.2023.112655

A Golgi-resident GPR108 cooperates with E3 ubiquitin ligase Smurf1 to suppress antiviral innate immunity

Cell Rep. 2023 Jun 27;42(6):112655. doi: 10.1016/j.celrep.2023.112655. Epub 2023 Jun 17.

Authors

Mengyuan Zhao¹, Yong Zhang², Lihua Qiang¹, Zhe Lu¹, Zhuo Zhao¹, Yesheng Fu³, Bo Wu³, Qiyao Chai⁴, Pupu Ge⁴, Zehui Lei¹, Xinwen Zhang¹, Bingxi Li⁴, Jing Wang⁴, Lingqiang Zhang⁵, Cui Hua Liu⁶

Affiliations

¹ CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing 101408, China.
² CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 100850, China; School of Medicine, Tsinghua University, Beijing 100084, China.
³ State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 100850, China.
⁴ CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
⁵ State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 100850, China. Electronic address: zhanglq@nic.bmi.ac.cn.
⁶ CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing 101408, China. Electronic address: liucuihua@im.ac.cn.

PMID: 37330913
DOI: 10.1016/j.celrep.2023.112655

Abstract

The regulation of antiviral immunity is crucial in maintaining host immune homeostasis, a process that involves dynamic modulations of host organelles. The Golgi apparatus is increasingly perceived as a host organelle functioning as a critical platform for innate immunity, but the detailed mechanism by which it regulates antiviral immunity remains elusive. Here, we identify the Golgi-localized G protein-coupled receptor 108 (GPR108) as a regulator of type Ι interferon responses by targeting interferon regulatory factor 3 (IRF3). Mechanistically, GPR108 enhances the ubiquitin ligase Smad ubiquitylation regulatory factor 1 (Smurf1)-mediated K63-linked polyubiquitination of phosphorylated IRF3 for nuclear dot 10 protein 52 (NDP52)-dependent autophagic degradation, leading to suppression of antiviral immune responses against DNA or RNA viruses. Taken together, our study provides insight into the crosstalk between the Golgi apparatus and antiviral immunity via a dynamic and spatiotemporal regulation of GPR108-Smurf1 axis, thereby indicating a potential target for treating viral infection.

Keywords: CP: Immunology; GPR108; Golgi apparatus; IRF3; Smurf1; antiviral innate immunity; autophagy; ubiquitination.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antiviral Agents* / metabolism
Golgi Apparatus / metabolism
Immunity, Innate
Receptors, G-Protein-Coupled* / metabolism
Ubiquitin-Protein Ligases* / metabolism
Ubiquitination

Substances

Antiviral Agents
Ubiquitin-Protein Ligases
Gpr108 protein, mouse
SMURF1 protein, human
Smurf1 protein, mouse
Receptors, G-Protein-Coupled