PXD062911

PXD062911 is an original dataset announced via ProteomeXchange.

Title	The BPAN disease protein WDR45 forms condensates with Caprin-1 to regulate stress granule disassembly
Description	Beta-propeller protein-associated neurodegeneration (BPAN) is a rare X-linked neurodegenerative disorder primarily caused by mutations in the WD repeat domain 45 (WDR45) gene. While WDR45 has traditionally been linked to autophagy, our study uncovers a previously unrecognized role for WDR45 as a critical regulator of stress granule (SG) disassembly, providing new insights into the pathogenesis of BPAN and related neurodegenerative diseases. We demonstrate that WDR45’s recruitment to SGs via phase separation with Caprin-1 and facilitates SG disassembly by competing with G3BP1 for Caprin-1 binding, thereby modulating the core SG network. BPAN-associated WDR45 mutations, particularly in the WD5 domain, disrupt phase separation properties and impair interaction with Caprin-1, resulting in delayed SG disassembly and correlating with earlier disease onset in BPAN patients. Furthermore, WDR45 depletion exacerbates the accumulation of ALS-associated pathological SGs, highlighting its role in mitigating pathological protein aggregation. Notably, iPSC-derived midbrain neurons from BPAN patients with WDR45 mutation exhibit delayed SG recovery, highlighting the clinical relevance of WDR45 in SG dynamics. These findings reveal a novel function of WDR45 in SG disassembly through its interaction with Caprin-1, providing critical insights into BPAN pathogenesis and identifying potential therapeutic targets for neurodegenerative diseases linked to SG dysregulation.
HostingRepository	iProX
AnnounceDate	2025-04-14
AnnouncementXML	Submission_2025-04-13_23:36:35.068.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Haohao Tang
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Ascend

Revision	Datetime	Status	ChangeLog Entry
0	2025-04-13 23:35:18	ID requested
⏵ 1	2025-04-13 23:36:35	announced

Dataset with its publication pending

submitter keyword: BPAN disease,Caprin-1,granule disassembly,

Yang Chen
contact affiliation	Peking University Health Science Center
contact email	chenyang1816185048@bjmu.edu.cn
lab head
Haohao Tang
contact affiliation	Peking University Health Science Center
contact email	Tanghaohao0987@163.com
dataset submitter

iProX dataset URI