PXD056240

PXD056240 is an original dataset announced via ProteomeXchange.

Title	The Role of the Co-Chaperone DNAJB11 in Polycystic Kidney Disease: Molecular Mechanisms and Cellular Origin of Cyst Formation
Description	Autosomal dominant polycystic kidney disease (ADPKD) is caused by muta1ons in PKD1 and PKD2, encoding polycystin-1 (PC1) and polycystin-2 (PC2), which are required for the regula1on of the renal tubular diameter. Loss of polycystin func1on results in cyst forma1on. Atypical forms of ADPKD are caused by mutations in genes encoding endoplasmic reticulum (ER)-resident proteins through mechanisms that are not well understood. Here, we investigate the func1on of DNAJB11, an ER co-chaperone associated with atypical ADPKD. We generated mouse models with constitutive and conditional Dnajb11 inactivation and Dnajb11-deficient renal epithelial cells to investigate the mechanism underlying autosomal dominant inheritance, the specific cell types driving cyst formation, and molecular mechanisms underlying DNAJB11-dependent polycystic kidney disease. We show that biallelic loss of Dnajb11 causes cystic kidney disease and fibrosis, mirroring human disease characteristics. In contrast to classical ADPKD, cysts predominantly originate from proximal tubules. Cyst formation begins in utero and the timing of Dnajb11 inactivation strongly influences disease severity. Furthermore, we identify impaired PC1 cleavage as a potential mechanism underlying DNAJB11-dependent cyst formation. Proteomic analysis of Dnajb11- and Pkd1-deficient cells reveals common and distinct pathways and dysregulated proteins, providing a foundation to better understand phenotypic differences between different forms of ADPKD.
HostingRepository	MassIVE
AnnounceDate	2024-11-12
AnnouncementXML	Submission_2024-11-12_06:32:38.013.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Stefan Tholen
SpeciesList	scientific name: Mus musculus; common name: house mouse; NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-25 07:17:03	ID requested
⏵ 1	2024-11-12 06:32:38	announced

no publication

submitter keyword: Autosomal Dominant Polycystic Kidney Disease (ADPKD), Cyst Formation, DNAJB11, PKD1

Michael Koettgen, MD
contact affiliation	Medical Center; University of Freiburg
contact email	michael.koettgen@uniklinik-freiburg.de
lab head
Stefan Tholen
contact affiliation	Uniklinik Freiburg
contact email	stefan.tholen@uniklinik-freiburg.de
dataset submitter

MassIVE dataset URI

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://massive.ucsd.edu/v08/MSV000095950/