PXD050122

PXD050122 is an original dataset announced via ProteomeXchange.

Title	YAP maintains the dynamics of TDP-43 condensates and antagonizes TDP-43 pathology
Description	Recent studies exploring the underlying pathomechanisms of amyotrophic lateral sclerosis (ALS), a fatal motor neuron disorder, have focused on biomolecular condensates, such as stress granules (SGs) and TDP-43 condensates. Our comprehension of the physicochemical processes that control the behavior of these condensates is still evolving. In this work, we reveal an unexpected function for YAP, a central component of the Hippo pathway, in regulating the dynamic behavior of SGs and TDP-43 condensates, a role that is independent of its transcriptional activity in Hippo pathway. We found that YAP can directly bind to the TB domain of TDP-43 through its N-terminal domain. This interaction promotes the homotypic multimerization and phase separation of TDP-43, while inhibiting its hyper- phosphorylation and solidification under stress conditions. Remarkably, YAP, whose mRNA level is reduced in ALS patients, is found to co-localize with pathological pTDP-43 aggregates in the cytoplasmic foci of ALS patient brains. Additionally, elevating YAP/Yorkie expression substantially reduces neurotoxicity in a TDP-43 transgenic fly model of ALS. Our findings highlight an unexpected chaperone-like role of YAP in managing ALS-associated biomolecular condensates, presenting significant implications for potential ALS treatments.
HostingRepository	iProX
AnnounceDate	2024-02-24
AnnouncementXML	Submission_2025-02-23_17:58:23.047.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jiaqi Zhang
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-02-25 21:48:03	ID requested
⏵ 1	2025-02-23 17:58:23	announced

Dataset with its publication pending

submitter keyword: Amyotrophic lateral sclerosis

condensation, Stress granules

Liquid-liquid phase separation

YAP

TDP-43

Bo Wang
contact affiliation	School of life sciences, Xiamen University
contact email	bowang@xmu.edu.cn
lab head
Jiaqi Zhang
contact affiliation	School of life sciences, Xiamen University
contact email	zhangjq641@nenu.edu.cn
dataset submitter

iProX dataset URI