The Six-Transmembrane Enzyme GDE2 Is Required for the Release of Molecularly Distinct Small Extracellular Vesicles from Neurons.

ABSTRACT: Extracellular vesicles (EVs) are implicated in a multitude of physiological and pathophysiological processes in the nervous system; however, their biogenesis and cargoes are not well defined. Glycerophosphodiester Phosphodiesterase 2 (GDE2 or GDPD5) is a six-transmembrane protein that cleaves the Glycosylphosphatidylinositol (GPI)-anchor that tethers some proteins to the membrane and has important roles in neurodevelopment and disease-relevant pathways of neuronal survival. We show here that GDE2 regulates the number of small EVs (sEVs) released from the cell surface of neurons via its GPI-anchor cleavage activity and contributes to the loading of protein cargo through enzymatic and non-enzymatic mechanisms. Proteomic profiling reveals that GDE2 releases at least two distinct EV population

SUBMITTER: Shuler KT 

PROVIDER: S-EPMC11394063 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature