PXD035302

PXD035302 is an original dataset announced via ProteomeXchange.

Title	Priming by IKKβ recruits NLRP3 to the trans-Golgi network to enable NEK7-independent inflammasome activation
Description	The NLRP3 inflammasome plays a central role in antimicrobial defense as well as in the context of sterile inflammatory conditions. NLRP3 activity is governed by two independent signals: The first signal primes NLRP3, rendering it responsive to the second signal, which then triggers inflammasome formation. Our understanding of how NLRP3 priming contributes to inflammasome activation remains limited. Here we show that IKKβ, a kinase activated during priming, induces recruitment of NLRP3 to phosphatidylinositol-4-phosphate (PI4P), a lipid enriched on the trans-Golgi network. Intriguingly, NEK7, a mitotic spindle kinase that had previously been thought to be indispensable for NLRP3 activation, was redundant for inflammasome formation when IKKβ recruited NLRP3 to PI4P. Studying iPSC-derived human macrophages revealed that the IKKβ-mediated NEK7-independent pathway constitutes the predominant NLRP3 priming mechanism in human myeloid cells. Our results suggest that PI4P binding represents a new type of "primed" state into which NLRP3 is brought by IKKβ activity.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:57:36.194.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sophia Mädler
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2022-07-13 07:55:12	ID requested
1	2022-11-17 05:15:32	announced
⏵ 2	2023-11-14 08:57:36	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: Human, LC-MSMS, Macrophages, Monocytes, Innate Immunity, NEK7, Pattern Recognition, Inflammasome, NLRP3

Veit Hornung
contact affiliation	Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, 81377 Munich, Germany
contact email	hornung@genzentrum.lmu.de
lab head
Sophia Mädler
contact affiliation	Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried 82152, Germany.
contact email	maedler@biochem.mpg.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/2022/11/PXD035302

PRIDE project URI

• PRIDE
  1. PXD035302
     1. Label: PRIDE project
     2. Name: Priming by IKKβ recruits NLRP3 to the trans-Golgi network to enable NEK7-independent inflammasome activation