{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Sindram E"],"funding":["Deutsche Forschungsgemeinschaft (DFG)","Bundesministerium für Bildung und Forschung","Center for Integrative Biological Signalling Studies","Deutsche Forschungsgemeinschaft","European Research Council","Europäische Konföderation der Oberrheinischen Universitäten (EUCOR)","Europäische Konföderation der Oberrheinischen Universitäten","Fritz Thyssen Stiftung","Hans A. Krebs, Faculty of Medicine, University Medical Center Freiburg","Bundesministerium für Bildung und Forschung (BMBF)","Fritz Thyssen Stiftung (Fritz Thyssen Foundation)","Medical Faculty, University of Freiburg"],"pagination":["4040-4071"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12373796"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["26(16)"],"pubmed_abstract":["Reduced autophagy is associated with the aberrant humoral response observed in lipopolysaccharide-responsive beige-like anchor protein (LRBA) deficiency; however, the molecular mechanisms and their impact on T-cell responses remain poorly understood. We identify two novel LRBA interactors, phosphoinositide 3-kinase regulatory subunit 4 (PIK3R4) and FYVE And Coiled-Coil Domain Autophagy Adaptor 1 (FYCO1), which each play key roles in autophagy. PIK3R4 facilitates the production of phosphatidylinositol-3 phosphate (PI(3)P) that promotes autophagosome formation and autophagosome-lysosome fusion, whereas FYCO1 supports autophagosome movement. LRBA-knockout (KO) cells show impaired PI(3)P production, reduced autophagosome-lysosome fusion, accumulation of enlarged autophagosomes, and decreased c"],"journal":["EMBO reports"],"pubmed_title":["LRBA deficiency impairs autophagy and contributes to enhanced antigen presentation and T-cell dysregulation."],"pmcid":["PMC12373796"],"funding_grant_id":["10.18.1.039MN","IFB/CCI: 01E01303","01GM1517C","ACTIv","403222702 - SFB 1381","GR1617/8-1","IMPATH-SFB SFB1160/2","Project Number 2021/B3-Fol","E-med SysINFLAME: 012X1306F","CIBSS - EXC-2189- Project ID 390939984","769065","Project Number 450392965","Project-IDs 450216812,409673687,SFB 1381 (Project ID 403222702),SFB 1177 (Project ID 259130777)","CIBSS-EXC-2189 Project ID 390939984"],"pubmed_authors":["Proietti M","Mishra P","Grimbacher B","Sindram E","Kraft C","Rambold A","Roussa E","Deau MC","Ruf S","Ligeon LA","Nestel S","Thedieck K","Gamez-Diaz L","Sanchez-Martin P","Gunther S","Jung S","Munz C"],"additional_accession":[]},"is_claimable":false,"name":"LRBA deficiency impairs autophagy and contributes to enhanced antigen presentation and T-cell dysregulation.","description":"Reduced autophagy is associated with the aberrant humoral response observed in lipopolysaccharide-responsive beige-like anchor protein (LRBA) deficiency; however, the molecular mechanisms and their impact on T-cell responses remain poorly understood. We identify two novel LRBA interactors, phosphoinositide 3-kinase regulatory subunit 4 (PIK3R4) and FYVE And Coiled-Coil Domain Autophagy Adaptor 1 (FYCO1), which each play key roles in autophagy. PIK3R4 facilitates the production of phosphatidylinositol-3 phosphate (PI(3)P) that promotes autophagosome formation and autophagosome-lysosome fusion, whereas FYCO1 supports autophagosome movement. LRBA-knockout (KO) cells show impaired PI(3)P production, reduced autophagosome-lysosome fusion, accumulation of enlarged autophagosomes, and decreased c","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Aug","modification":"2026-05-08T10:46:36.413Z","creation":"2026-04-07T23:47:27.644Z"},"accession":"S-EPMC12373796","cross_references":{"pubmed":["40550954"],"doi":["10.1038/s44319-025-00504-7"]}}