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VAMP7 KO and ATG5 KO in axonal growth

ABSTRACT: VAMP7 is involved in autophagy and in exocytosis mediating neurite growth, two yet unconnected cellular pathways. Here we found that nutrient restriction and activation of autophagy stimulated axonal growth while inhibition led to multiple axons. VAMP7 KO neuronal cells showed impaired whereas ATG5 KO cells showed increased neurite growth. Secretomics identified that ER-phagy-related LC3 interacting region-containing proteins Atlastins and Reticulons were more abundant in ATG5 KO and less abundant in VAMP7 KO secretomes. The secretion of reticulon 3, LC3-II and P62 was impaired in VAMP7 KO cells. Treatment of neuronal cells with ATG5 or VAMP7 KO conditioned medium showed no effect thus the role of ATG5 and VAMP7 in neurite growth was cell autonomous. A nanobody directed against VAMP7 inhibited axonal growth induced by nutrient restriction. Furthermore, expression of the inhibitory Longin domain of VAMP7 impaired the subcellular localization of reticulon 3 in neurons. We propose that VAMP7-dependent unconventional autophagy-dependent secretion is an essential mechanism for axonal growth.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Rattus Norvegicus (rat)

SUBMITTER: Chiara guerrera

LAB HEAD: Chiara Guerrera

PROVIDER: PXD020502 | Pride | 2021-03-29

REPOSITORIES: Pride

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