PXD058416

PXD058416 is an original dataset announced via ProteomeXchange.

Title	STING-mediated proton channel activity, signaling, and autoimmune disease require ArfGAP2
Description	STING transmits signals downstream of the cytosolic DNA sensor cGAS, leading to transcriptional up-regulation of cytokines. However, components of the STING signaling pathway, such as IRF3 and IFNAR1, are not essential for autoinflammatory disease in STING gain-of-function (SAVI) mice. Recent findings indicate that STING can also function as a proton channel that deacidifies the Golgi. Since pH impacts Golgi enzyme activity, protein maturation, and trafficking, we hypothesized that STING proton channel activity influences multiple Golgi functions. Here, we show that STING-mediated proton efflux non-transcriptionally regulates Golgi trafficking of protein cargos. This process requires the Golgi-associated protein ArfGAP2, a cell type-specific dual regulator of STING-mediated proton efflux and signaling. Deletion of ArfGAP2 in hematopoietic and endothelial cells markedly reduces STING-mediated cytokine and chemokine secretion, immune cell activation, and autoinflammatory pathology in SAVI mice. Thus, ArfGAP2 facilitates STING-mediated signaling and cytokine release in hematopoietic cells, significantly contributing to autoinflammatory disease pathogenesis.
HostingRepository	PRIDE
AnnounceDate	2024-11-30
AnnouncementXML	Submission_2024-11-30_08:13:37.211.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hossein Fazelinia
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	3-(carboxamidomethylthio)propanoylated residue
Instrument	LTQ; Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-11-29 07:47:58	ID requested
⏵ 1	2024-11-30 08:13:37	announced

Dataset with its publication pending

submitter keyword: ArfGAP2, antiviral immunity, interferon, cGAS, cytokines, SAVI,STING, chemokines, autoinflammation

Jonathan Miner,
contact affiliation	Associate Professor of Medicine: Rheumatology Chair, Gene Therapy and Vaccines Graduate Program Director, RVCL Research Center University of Pennsylvania Perelman School of Medicine
contact email	jonathan.miner@pennmedicine.upenn.edu
lab head
Hossein Fazelinia
contact affiliation	Children's Hospital of Philadelphia
contact email	fazeliniah@email.chop.edu
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/2024/11/PXD058416

PRIDE project URI

• PRIDE
  1. PXD058416
     1. Label: PRIDE project
     2. Name: STING-mediated proton channel activity, signaling, and autoimmune disease require ArfGAP2