ESCRT disruption provides evidence against trans-synaptic signaling via extracellular vesicles.
J Cell Biol
; 223(9)2024 Sep 02.
Article
em En
| MEDLINE
| ID: mdl-38842573
ABSTRACT
Extracellular vesicles (EVs) are released by many cell types, including neurons, carrying cargoes involved in signaling and disease. It is unclear whether EVs promote intercellular signaling or serve primarily to dispose of unwanted materials. We show that loss of multivesicular endosome-generating endosomal sorting complex required for transport (ESCRT) machinery disrupts release of EV cargoes from Drosophila motor neurons. Surprisingly, ESCRT depletion does not affect the signaling activities of the EV cargo Synaptotagmin-4 (Syt4) and disrupts only some signaling activities of the EV cargo evenness interrupted (Evi). Thus, these cargoes may not require intercellular transfer via EVs, and instead may be conventionally secreted or function cell-autonomously in the neuron. We find that EVs are phagocytosed by glia and muscles, and that ESCRT disruption causes compensatory autophagy in presynaptic neurons, suggesting that EVs are one of several redundant mechanisms to remove cargoes from synapses. Our results suggest that synaptic EV release serves primarily as a proteostatic mechanism for certain cargoes.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sinapses
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Transdução de Sinais
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Proteínas de Drosophila
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Drosophila melanogaster
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Complexos Endossomais de Distribuição Requeridos para Transporte
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Vesículas Extracelulares
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Neurônios Motores
Limite:
Animals
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article