PXD063206-1

PXD063206 is an original dataset announced via ProteomeXchange.

Title	Maintenance of neuronal TDP-43 expression requires axonal lysosome transport
Description	TDP-43 mislocalization and pathology occurs across a range of neurodegenerative diseases, but the pathways that modulate TDP-43 in neurons are not well understood. We generated a Halo-TDP-43 knock-in iPSC line and performed a genome-wide CRISPR interference FACS-based screen to identify modifiers of TDP-43 levels in neurons. A meta-analysis of our screen and publicly available screens identified both specific hits and pathways present across multiple screens, the latter likely responsible for generic protein level maintenance. We identified BORC, a complex required for anterograde lysosome transport, as a specific modifier of TDP-43 iP lysosome location is required for proper protein turnover. As such, lysosome location and function are crucial for maintaining TDP-43 protein levels in neurons.
HostingRepository	PRIDE
AnnounceDate	2025-08-01
AnnouncementXML	Submission_2025-08-01_14:32:53.410.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yue Andy Qi
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2025-04-22 17:18:41	ID requested
⏵ 1	2025-08-01 14:32:54	announced

10.1101/2024.09.30.615241;

Ryan VH, Lawton S, Reyes JF, Hawrot J, Frankenfield AM, Seddighi S, Ramos DM, Epstein J, Faghri F, Johnson NL, Zou J, Kampmann M, Replogle J, Qi YA, Yuan H, Johnson KR, Maric D, Hao L, Nalls MA, Ward ME, Maintenance of neuronal TDP-43 expression requires axonal lysosome transport. bioRxiv, ():(2025) [pubmed]

submitter keyword: iPSC neurons TDP43

Veronica Ryan
contact affiliation	Center for Alzheimer's and Related Dementias (CARD), NIA and NINDS, NIH, Bethesda, Maryland, USA.
contact email	veronica.ryan@nih.gov
lab head
Yue Andy Qi
contact affiliation	Center for Alzheimer’s Disease and Related Dementias (CARD)/NIH
contact email	andy.qi@nih.gov
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/2025/08/PXD063206

PRIDE project URI

• PRIDE
  1. PXD063206
     1. Label: PRIDE project
     2. Name: Maintenance of neuronal TDP-43 expression requires axonal lysosome transport