Presenilins as hub proteins controlling the endocytic and autophagic pathways and small extracellular vesicle secretion.

ABSTRACT: Emerging evidence indicates that autophagy is tightly connected to the endocytic pathway. Here, we questioned the role of presenilins (PSENs 1 and 2), previously shown to be involved in autophagy regulation, in the secretion of small endocytic-originating extracellular vesicles known as exosomes. Indeed, while wild-type cells responded to stimuli promoting both multivesicular endosome (MVE) formation and secretion of small extracellular vesicles (sEVs) enriched in canonical exosomal proteins, PSEN-deficient cells were almost unaffected to these stimuli. Moreover, in PSEN-deficient cells, the re-expression of either PSEN1 or the functional active PSEN1delta9 mutant led to a rescue of most sEV secretion, while the deletion of PSEN1 alone almost fully phenocopied total PSEN invalidation. We f

SUBMITTER: Lauritzen I 

PROVIDER: S-EPMC11735957 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature