PXD051912-1

PXD051912 is an original dataset announced via ProteomeXchange.

Title	DLG1 functions upstream of SDCCAG3 and IFT20 to control ciliary targeting of polycystin-2
Description	Polarized vesicular trafficking directs specific receptors and ion channels to cilia, but the underlying mechanisms are poorly understood. Here we describe a role for DLG1, a core component of the Scribble polarity complex, in regulating ciliary protein trafficking in kidney epithelial cells. Conditional knockout of Dlg1 in mouse kidney caused causes ciliary elongation and cystogenesis, and cell-based proximity labelling proteomics and fluorescence microscopy showed alterations in the ciliary proteome upon loss of DLG1. Specifically, the retromer-associated protein SDCCAG3, IFT20 and polycystin-2 (PC2) were are reduced in cilia of DLG1 deficient cells compared to control cells. This phenotype was is recapitulated in vivo and rescuable by re-expression of wildtype DLG1, but not a Congenital Anomalies of the Kidney and Urinary Tract (CAKUT)-associated DLG1 variant, p.T489R. Finally, biochemical approaches and Alpha Fold modelling suggested that SDCCAG3 and IFT20 form a complex that associates, at least indirectly, with DLG1. Our work identifies a key role for DLG1 in regulating ciliary protein composition and suggests that ciliary dysfunction of the p.T489R DLG1 variant may contribute to CAKUT.
HostingRepository	PRIDE
AnnounceDate	2024-05-14
AnnouncementXML	Submission_2024-05-14_15:37:51.301.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Karsten Boldt
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2024-04-30 22:59:03	ID requested
⏵ 1	2024-05-14 15:37:51	announced
2	2024-10-22 06:39:19	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: DLG1, BioID2, primary cilia

Dr. Karsten Boldt
contact affiliation	Core Facility for Medical Proteomics and Institute for Ophthalmic Research Eberhard-Karls University of Tuebingen
contact email	karsten.boldt@uni-tuebingen.de
lab head
Karsten Boldt
contact affiliation	Medical Bioanalytics
contact email	karsten.boldt@uni-tuebingen.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/2024/05/PXD051912

PRIDE project URI

• PRIDE
  1. PXD051912
     1. Label: PRIDE project
     2. Name: DLG1 functions upstream of SDCCAG3 and IFT20 to control ciliary targeting of polycystin-2