Local regulation of extracellular vesicle traffic by the synaptic endocytic machinery.

ABSTRACT: Neuronal extracellular vesicles (EVs) are locally released from presynaptic terminals, carrying cargoes critical for intercellular signaling and disease. EVs are derived from endosomes, but it is unknown how these cargoes are directed to the EV pathway rather than for conventional endolysosomal degradation. Here, we find that endocytic machinery plays an unexpected role in maintaining a release-competent pool of EV cargoes at synapses. Endocytic mutants, including nervous wreck (nwk), shibire/dynamin, and AP-2, unexpectedly exhibit local presynaptic depletion specifically of EV cargoes. Accordingly, nwk mutants phenocopy synaptic plasticity defects associated with loss of the EV cargo synaptotagmin-4 (Syt4) and suppress lethality upon overexpression of the EV cargo amyloid precursor protei

SUBMITTER: Blanchette CR 

PROVIDER: S-EPMC8952828 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature