PXD045934

PXD045934 is an original dataset announced via ProteomeXchange.

Title	RHBDL4-triggered downregulation of COPII adaptor protein TMED7 suppresses TLR4-mediated inflammatory signaling
Description	The toll-like receptor 4 (TLR4) is a central regulator of innate immune signaling that primarily recognizes bacterial lipopolysaccharide (LPS) cell wall constituents to trigger cytokine secretion. We identify the intramembrane protease RHBDL4 as a negative regulator of TLR4 signaling. We show that RHBDL4-triggers the degradation of TLR4’s trafficking factor TMED7, a member of the p24 family of COPII adaptor proteins, which counteracts the transport of TLR4 to the cell surface. Besides TMED7, RHBDL4 cleaves a subset of related p24 cargo receptors, suggesting that this is a general protein abundance control mechanism to regulate the loading of specific secretory proteins into COPII vesicles. Notably, TLR4 activation by LPS mediates transcriptional upregulation of RHBDL4. Hence, TLR4 activation triggers an RHBDL4-dependent negative feedback loop to reduce the export of newly synthesized TLR4 molecules from the endoplasmic reticulum into COPII-coated vesicles. This secretory cargo tuning mechanism prevents the over-activation of TLR4-dependent signaling and consequently alleviates septic shock in a mouse model.
HostingRepository	PRIDE
AnnounceDate	2024-01-09
AnnouncementXML	Submission_2024-01-09_09:13:59.595.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Thomas Ruppert
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2023-10-06 10:11:53	ID requested
⏵ 1	2024-01-09 09:13:59	announced

Dataset with its publication pending

submitter keyword: intramembrane proteolysis, protein homeostasis, rhomboid-family proteins,Organelle proteomics, ER-associated degradation, protein trafficking

Thomas Ruppert
contact affiliation	Heidelberg University Centre for molecular biology (ZMBH) Im Neuenheimer Feld 282 69120 Heidelberg Germany
contact email	t.ruppert@zmbh.uni-heidelberg.de
lab head
Thomas Ruppert
contact affiliation	ZMBH, Im Neuenheimer Feld 282, 69122 Heidelberg
contact email	t.ruppert@zmbh.uni-heidelberg.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/2024/01/PXD045934

PRIDE project URI

• PRIDE
  1. PXD045934
     1. Label: PRIDE project
     2. Name: RHBDL4-triggered downregulation of COPII adaptor protein TMED7 suppresses TLR4-mediated inflammatory signaling