PXD074819

PXD074819 is an original dataset announced via ProteomeXchange.

Title	Regulation of the PKD2 channel function and associated disease phenotypes by RASSF4
Description	Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common monogenic genetic disorders, caused by mutations in receptor PKD1 or ion channel PKD2, and is characterized by progressive renal cyst development with additional hepatic and extrarenal manifestations. As effective treatments for ADPKD remain limited, further investigation into the function and regulation of PKD proteins is needed. Using biotin-based proximity labeling combined with mass spectrometry in human embryonic kidney (HEK) cells, here we identify Ras association domain family member 4 (RASSF4) as a potential PKD2-interacting protein. The association between PKD2 and RASSF4 is validated by co-immunoprecipitation, bimolecular fluorescence complementation, and in vitro binding assays in HEK cells and mouse kidneys. Functional analyses using two-electrode voltage clamp electrophysiology in Xenopus oocytes demonstrate that RASSF4 enhances PKD2 channel activity without affecting its membrane expression. In vivo studies in larval zebrafish show that RASSF4 over-expression alleviates, whereas Rassf4 knockdown exacerbates, Pkd2 knockdown–associated phenotypes, including tail curling, pronephric cyst formation, renal filtration defects, and motor dysfunction. Disruption of the RASSF4–PKD2 interaction using a blocking peptide (aa P134–S168) abolishes RASSF4-mediated stimulation of PKD2 channel function and phenotypic rescue, while worsening disease severity, likely by interfering with endogenous complex formation. Mechanistically, RASSF4 enhances the functionally critical intramolecular interaction between the PKD2 N- and C-termini and suppresses RAS/MAPK signaling in HEK cells. Together, these findings identify RASSF4 as a PKD2 regulator and suggest that RASSF4/PKD2 complex formation represents a potential therapeutic target for ADPKD
HostingRepository	iProX
AnnounceDate	2026-02-13
AnnouncementXML	Submission_2026-02-24_18:10:07.562.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Rui Tian
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2026-02-24 18:09:44	ID requested
⏵ 1	2026-02-24 18:10:08	announced

Dataset with its publication pending

submitter keyword: ADPKD, electrophysiology, oocyte, mammalian cell, zebrafish, blocking peptide

Xingzhen Chen
contact affiliation	University of Alberta
contact email	xzchen@ualberta.ca
lab head
Rui Tian
contact affiliation	Hubei University of Technology
contact email	hutrtianrui@163.com
dataset submitter

iProX dataset URI