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| Item Type: | Preprint | ||||
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| 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 Lucht, M.T. and Krause, E. and Schmitz, D. and Haucke, V. | ||||
| Abstract: | Information processing in the brain is encoded as electrical impulses in neurons that are relayed from the presynaptic compartment to postsynaptic neurons by regulated neurotransmitter release. Neurons are known to rely on autophagy for the removal of defective proteins or organelles to maintain synaptic neurotransmission and to 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 the 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 in which neuronal autophagy controls axonal ER calcium stores to regulate neurotransmission in healthy neurons and in the brain. | ||||
| Keywords: | Animals, Mice | ||||
| Source: | bioRxiv | ||||
| Publisher: | Cold Spring Harbor Laboratory Press | ||||
| Article Number: | 2020.07.06.189522 | ||||
| Date: | 6 July 2020 | ||||
| Official Publication: | https://doi.org/10.1101/2020.07.06.189522 | ||||
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