PXD039411

PXD039411 is an original dataset announced via ProteomeXchange.

Title	STING signalling is terminated through ESCRT-dependent microautophagy of vesicles originating from recycling endosomes
Description	Stimulator of interferon genes (STING) is essential for the type I interferon response against a variety of DNA pathogens. Upon emergence of cytosolic DNA, STING translocates from the endoplasmic reticulum (ER) to the Golgi where STING activates the downstream kinase TBK1, then to lysosome through recycling endosomes (REs) for its degradation. Although the molecular machinery of STING activation is extensively studied and defined, the one underlying STING degradation and inactivation has not yet been fully elucidated. Here we show that STING is degraded by the endosomal sorting complexes required for transport (ESCRT)-driven microautophagy. Airyscan super-resolution microscopy and correlative light/electron microscopy suggest that STING-positive vesicles of an RE origin are directly encapsulated into Lamp1-positive compartments. Screening of mammalian Vps genes, the yeast homologues of which regulate Golgi-to-vacuole transport, shows that ESCRT proteins are essential for the STING encapsulation into Lamp1-positive compartments. Knockdown of Tsg101 and Vps4, components of ESCRT, results in the accumulation of STING vesicles in the cytosol, leading to the sustained type I interferon response. Knockdown of Tsg101 in human primary T cells leads to an increase the expression of interferon-stimulated genes. STING undergoes K63-linked ubiquitination at lysine 288 during its transit through the Golgi/REs, and this ubiquitination is required for STING degradation. Our results reveal a molecular mechanism that prevents hyperactivation of innate immune signalling, which operates at REs.
HostingRepository	PRIDE
AnnounceDate	2023-01-24
AnnouncementXML	Submission_2023-01-24_15:43:38.501.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD039411
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	TakehiroSuzuki
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	S-carboxamidoethyl-L-cysteine; palmitoylated residue; phosphorylated residue; myristoylated residue; acetylated residue; monohydroxylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-01-13 06:46:22	ID requested
⏵ 1	2023-01-24 15:43:38	announced

10.6019/PXD039411;

submitter keyword: microautophagy,STING, ESCRT

NaoshiDohmae
contact affiliation	Biomolecular characterization unit, Center for Sustainable Resource Science, RIKEN
contact email	dohmae@riken.jp
lab head
TakehiroSuzuki
contact affiliation	RIKEN Center for Sustainable Resource Science
contact email	takehirosuzuki@riken.jp
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/01/PXD039411

PRIDE project URI

• PRIDE
  1. PXD039411
     1. Label: PRIDE project
     2. Name: STING signalling is terminated through ESCRT-dependent microautophagy of vesicles originating from recycling endosomes