Recent progress on the activation of the cGAS-STING pathway and its regulation by biomolecular condensation

8Citations
Citations of this article
10Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

The cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthetase (cGAS)-stimulator of interferon genes (STING) pathway, comprising the DNA sensor cGAS, the second messenger cyclic GMP-AMP (cGAMP), and the endoplasmic reticulum (ER) adaptor protein STING, detects cytoplasmic double-stranded DNA (dsDNA) to trigger type I-interferon responses for host defense against pathogens. Previous studies defined a model for the allosteric activation of cGAS by DNA-binding, but recent work reveals other layers of mechanisms to regulate cGAS activation such as the phase condensation and metal ions, especially the discovery of Mn2+ as a cGAS activator. Activation of the 2′3′-cGAMP sensor STING requires translocating from the ER to the Golgi apparatus. The sulfated glycosaminoglycans at the Golgi are found to be the second STING ligand promoting STING oligomerization and activation in addition to 2′3′-cGAMP, while surpassed levels of 2′3′-cGAMP induce ER-located STING to form a highly organized ER membranous condensate named STING phase-separator to restrain STING activation. Here, we summarize recent advances in the regulation of cGAS-STING activation and their implications in physiological or pathological conditions, particularly focusing on the emerging complexity of the regulation.

Cite

CITATION STYLE

APA

Yu, X., Zhao, Z., & Jiang, Z. (2022, June 1). Recent progress on the activation of the cGAS-STING pathway and its regulation by biomolecular condensation. Journal of Molecular Cell Biology. Oxford University Press. https://doi.org/10.1093/jmcb/mjac042

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free