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VAMP7-dependent autophagic secretion allows for axonal resilience in growth restricting conditions.VAMP7-dependent autophagic secretion allows for axonal resilience in growth restricting conditions.

ABSTRACT: VAMP7 is involved in autophagy and exocytosis mediating neurite growth, two yet unconnected cellular pathways. Here we show the occurrence of combined VAMP7/ATG9 secretory events. VAMP7 localized, together with LC3 and ATG9, in vesicles moving anterogradely along the axon towards growth cones. VAMP7 knockout disrupted the autophagy response to drugs and starvation. Release of extracellular vesicles triggered by autophagy was impaired in VAMP7-knockout cells and autophagy-deficient cells were impaired in VAMP7 exocytosis. Secretomics showed that VAMP7-knockout cells were impaired in unconventional secretion of cytoplasmic, exosomal and mitochondrial proteins. We further found that autophagy stimulated neurite growth in a VAMP7-dependent manner. Furthermore, neurons still grew long axons in nutrient-restricted conditions and when treated with autophagy-inducing drugs. A nanobody directed against VAMP7 inhibited the effect of nutrient restriction. We propose that VAMP7-dependent autophagic secretion contributes to a resilience mechanism to preserve axonal growth in restriction conditions, as part of brain sparing occurring in growth restriction.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Rattus Norvegicus (rat)

SUBMITTER: Chiara guerrera

LAB HEAD: GUERRERA Ida Chiara

PROVIDER: PXD014231 | Pride | 2020-12-10

REPOSITORIES: Pride

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			Action	DRS
	20180713_ThGA_KO_lysat_tot_2_7907.raw	Raw
	20180713_ThGA_KO_lysat_tot_3_7908.raw	Raw
	20180713_ThGA_WT_lysat_tot_2_7912.raw	Raw
	20180713_ThGA_WT_lysat_tot_3_7913.raw	Raw
	20180719_ThGA_KO_surnageant_tot_1_7941_180721164614.raw	Raw

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