{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Ryan VH"],"funding":["National Institute of Neurological Disorders and Stroke","NIA NIH HHS","NINDS NIH HHS","National Institute of General Medical Sciences","NIGMS NIH HHS","National Institute on Aging"],"pagination":["RP104057"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12448747"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["14"],"pubmed_abstract":["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 human induced pluripotent stem cell (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 protein, but not mRNA, levels in neurons. BORC loss led to longer half-life of TDP-43 and other proteins, suggesting lyso"],"journal":["eLife"],"pubmed_title":["Maintenance of neuronal TDP-43 expression requires axonal lysosome transport."],"pmcid":["PMC12448747"],"funding_grant_id":["Fi2GM142475","R01NS121608","R01 NS121608","Intramural Research Program"],"pubmed_authors":["Maric D","Zou J","Johnson K","Ward ME","Hao L","Ramos DM","Yuan H","Johnson NL","Kampmann M","Qi YA","Replogle J","Lawton S","Frankenfield AM","Seddighi S","Faghri F","Ryan VH","Reyes JF","Epstein J","Nalls MA","Hawrot J"],"additional_accession":[]},"is_claimable":false,"name":"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 human induced pluripotent stem cell (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 protein, but not mRNA, levels in neurons. BORC loss led to longer half-life of TDP-43 and other proteins, suggesting lyso","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Sep","modification":"2026-06-03T14:39:25.737Z","creation":"2026-05-29T03:05:33.921Z"},"accession":"S-EPMC12448747","cross_references":{"pubmed":["40970386"],"doi":["10.7554/eLife.104057"]}}