LRBA deficiency impairs autophagy and contributes to enhanced antigen presentation and T-cell dysregulation.

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

SUBMITTER: Sindram E 

PROVIDER: S-EPMC12373796 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature