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Role of VAMP7-Dependent Secretion of Reticulon 3 in Neurite Growth

Abstract : VAMP7 is involved in autophagy and in exocytosis-mediated neurite growth, two yet unconnected cellular pathways. Here, we find that nutrient restriction and activation of autophagy stimulate axonal growth, while autophagy inhibition leads to loss of neuronal polarity. VAMP7 knockout (KO) neuronal cells show impaired neurite growth, whereas this process is increased in autophagy-null ATG5 KO cells. We find that endoplasmic reticulum (ER)-phagy-related LC3-interacting-region-containing proteins Atlastin 3 and Reticulon 3 (RTN3) are more abundant in autophagy-related protein ATG5 KO and less abundant in VAMP7 KO secretomes. Treatment of neuronal cells with ATG5 or VAMP7 KO conditioned medium does not recapitulate the effect of these KOs on neurite growth. A nanobody directed against VAMP7 inhibits axonal overgrowth induced by nutrient restriction. Furthermore, expression of the inhibitory Longin domain of VAMP7 impairs the subcellular localization of RTN3 in neurons. We propose that VAMP7-dependent secretion of RTN3 regulates neurite growth.
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https://www.hal.inserm.fr/inserm-03090746
Contributor : Clara Martinez Rico <>
Submitted on : Wednesday, December 30, 2020 - 9:17:27 AM
Last modification on : Wednesday, June 2, 2021 - 4:26:27 PM
Long-term archiving on: : Wednesday, March 31, 2021 - 6:13:44 PM

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Wojnacki et al. Cell Rep. 2020...
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José Wojnacki, Sébastien Nola, Philippe Bun, Béatrice Cholley, Francesca Filippini, et al.. Role of VAMP7-Dependent Secretion of Reticulon 3 in Neurite Growth. Cell Reports, Elsevier Inc, 2020, 33 (12), pp.108536. ⟨10.1016/j.celrep.2020.108536⟩. ⟨inserm-03090746⟩

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