PXD041652

PXD041652 is an original dataset announced via ProteomeXchange.

Title	E-selectin-mediated rapid NLRP3 inflammasome activation regulates S100A8/A9 release from neutrophils via transient gasdermin D pore formation
Description	S100A8/A9 is a proinflammatory mediator released by myeloid cells during many acute and chronic inflammatory disorders. However, the precise mechanism of its release from the cytosolic compartment of neutrophils is still elusive. We report here that E-selectin-induced rapid S100A8/A9 release during inflammation occurs in a NLRP3 inflammasome-dependent fashion. Mechanistically, E-selectin engagement triggers Bruton?s tyrosine kinase dependent tyrosine phosphorylation of NLRP3. Concomitant potassium efflux via the voltage-gated potassium channel KV1.3 mediates ASC oligomerization. This is followed by caspase-1 cleavage and downstream activation of pore forming gasdermin D, enabling cytosolic S100A8/A9 to be released. Strikingly, E-selectin-mediated gasdermin D pore formation does not result in cell death, but is a transient process involving activation of the ESCRT-III membrane repair machinery. These findings do not only elucidate the molecular mechanisms of controlled S100A8/A9 release but also identify the NLRP3/gasdermin D axis as a rapid and reversible activation system in neutrophils during inflammation.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:12:33.819.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sebastian Kallabis
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-04-19 08:13:40	ID requested
1	2023-10-25 02:06:28	announced
⏵ 2	2023-11-14 09:12:34	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: Neutrophile, Inflammation,Gasdermin D, transient pore formation

Prof. Dr.
contact affiliation	Walter Brendel Center of Experimental Medicine Institute of Cardiovascular Physiology and Pathophysiology Biomedizinisches Centrum München Ludwig-Maximilians-Universität Großhaderner Str. 9 82152 Planegg-Martinsried GERMANY
contact email	markus.sperandio@lmu.de
lab head
Sebastian Kallabis
contact affiliation	Department for Systems Immunology & Proteomics Institute of Innate Immunity University Hospital Bonn Venusberg - Campus 1 53127 Bonn Germany
contact email	kallabis@uni-bonn.de
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/2023/10/PXD041652

PRIDE project URI

• PRIDE
  1. PXD041652
     1. Label: PRIDE project
     2. Name: E-selectin-mediated rapid NLRP3 inflammasome activation regulates S100A8/A9 release from neutrophils via transient gasdermin D pore formation