Journal
NEURON
Volume 109, Issue 2, Pages 299-+Publisher
CELL PRESS
DOI: 10.1016/j.neuron.2020.10.005
Keywords
-
Categories
Funding
- European Union [H2020-MSCA, 655604-SYNPT]
- European Research Council (an ERC synergy grant )
- Deutsche Forschungsgemeinschaft (DFG
- German Research Foundation) under Germany's Excellence Strategy [EXC-2049-390688087]
- Reinhart Koselleck Program [HA2685/13-1]
- Leibniz SAW Program [SAW-2014-FMP-2 359]
- Bundesministerium fur Bildung und Forschung [Smartage 01GQ1420B, Smartage 01GQ1420C]
Ask authors/readers for more resources
This study demonstrates that loss of neuronal autophagy leads to selective accumulation of tubular endoplasmic reticulum (ER) in axons, resulting in increased excitatory neurotransmission and compromised postnatal viability in vivo. The elevated excitatory neurotransmission is caused by increased calcium release from ER stores via ryanodine receptors accumulated in axons and at presynaptic sites. Neuronal autophagy controls axonal ER calcium stores to regulate neurotransmission in healthy neurons and in the brain.
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available