2. Academic Validation
  3. Trans-Golgi network tethering factors regulate TBK1 trafficking and promote the STING-IFN-I pathway

Trans-Golgi network tethering factors regulate TBK1 trafficking and promote the STING-IFN-I pathway

  • Cell Discov. 2025 Mar 18;11(1):23. doi: 10.1038/s41421-024-00763-z.
Jinrui Wang # 1,  Shenghui Niu # 1,  Xiao Hu 1,  Tianxing Li 1,  Shengduo Liu 2,  Yingfeng Tu 1,  Zehua Shang 1,  Lin Zhao 1,  Pinglong Xu 2,  Jingwen Lin 1,  Lu Chen 1,  Daniel D Billadeau 3,  Da Jia 4 5
Affiliations

Affiliations

  • 1 Key Laboratory of Birth Defects and Related Diseases of Women and Children, Department of Pediatrics, West China Second University Hospital, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, Sichuan, China.
  • 2 MOE Laboratory of Biosystems Homeostasis and Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang, China.
  • 3 Division of Oncology Research and Schulze Center for Novel Therapeutics, Mayo Clinic, Rochester, MN, USA.
  • 4 Key Laboratory of Birth Defects and Related Diseases of Women and Children, Department of Pediatrics, West China Second University Hospital, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, Sichuan, China. JiaDa@scu.edu.cn.
  • 5 Development and Related Diseases of Women and Children Key Laboratory of Sichuan Province, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China. JiaDa@scu.edu.cn.
  • # Contributed equally.
PMID: 40097395 DOI: 10.1038/s41421-024-00763-z
Abstract

The cGAS-STING pathway mediates the innate immune response to cytosolic DNA, contributing to surveillance against microbial invasion or cellular damage. Once activated, STING recruits TBK1 at the trans-Golgi network (TGN), which in turn phosphorylates IRF3 to induce type I interferon (IFN-I) expression. In contrast to STING, little is known about how TBK1 is transported to the TGN for activation. Here, we show that multiple TGN tethering factors, a group of proteins involved in vesicle capturing, are indispensable for STING-IFN-I signaling. Deletion of TBC1D23, a recently reported tethering factor, in mice impairs the STING-IFN-I signaling, but with insignificant effect on STING-NF-κB signaling. Mechanistically, TBC1D23 interacts with TBK1 via the WASH complex subunit FAM21 and promotes its endosome-to-TGN translocation. Furthermore, multiple TGN tethering factors were reduced in aged mice and senescent fibroblasts. In summary, our study uncovers that TGN tethering factors are key regulators of the STING-IFN-I signaling and suggests that their reduction in senescence may produce aberrant STING signaling.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z