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| Item Type: | Article |
|---|---|
| Title: | Neuronal autophagy regulates presynaptic neurotransmission by controlling the axonal endoplasmic reticulum |
| Creators Name: | Kuijpers, M., Kochlamazashvili, G., Stumpf, A., Puchkov, D., Swaminathan, A., Lucht, M.T., Krause, E., Maritzen, T., 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 |
| Volume: | 109 |
| Number: | 2 |
| Page Range: | 299-313 |
| Date: | 20 January 2021 |
| Additional Information: | Erratum in: Neuron 110(4): 734. |
| Official Publication: | https://doi.org/10.1016/j.neuron.2020.10.005 |
| PubMed: | View item in PubMed |
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