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Neuronal autophagy regulates presynaptic neurotransmission by controlling the axonal endoplasmic reticulum

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Item Type:Article
Title:Neuronal autophagy regulates presynaptic neurotransmission by controlling the axonal endoplasmic reticulum
Creators Name:Kuijpers, M. and Kochlamazashvili, G. and Stumpf, A. and Puchkov, D. and Swaminathan, A. and Lucht, M.T. and Krause, E. and Maritzen, T. and Schmitz, D. and Haucke, V.
Abstract:Neurons are known to rely on autophagy for removal of defective proteins or organelles to maintain synaptic neurotransmission and counteract neurodegeneration. In spite of its importance for neuronal health, the physiological substrates of neuronal autophagy in the absence of proteotoxic challenge have remained largely elusive. We use knockout mice conditionally lacking the essential autophagy protein ATG5 and quantitative proteomics to demonstrate that loss of neuronal autophagy causes selective accumulation of tubular endoplasmic reticulum (ER) in axons, resulting in increased excitatory neurotransmission and compromised postnatal viability in vivo. The gain in excitatory neurotransmission is shown to be a consequence of elevated calcium release from ER stores via ryanodine receptors accumulated in axons and at presynaptic sites. We propose a model where neuronal autophagy controls axonal ER calcium stores to regulate neurotransmission in healthy neurons and in the brain.
Keywords:Autophagy, ERphagy, Presynapse, Neurotransmission, Endoplasmic Reticulum, Calcium, Ryanodine Receptor, Animals, Mice
Source:Neuron
ISSN:0896-6273
Publisher:Cell Press
Date:5 November 2020
Official Publication:https://doi.org/10.1016/j.neuron.2020.10.005
PubMed:View item in PubMed
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https://edoc.mdc-berlin.de/19141/Preprint version

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