RRC ID 64005
Author Kuijpers M, Kochlamazashvili G, Stumpf A, Puchkov D, Swaminathan A, Lucht MT, Krause E, Maritzen T, Schmitz D, Haucke V.
Title Neuronal Autophagy Regulates Presynaptic Neurotransmission by Controlling the Axonal Endoplasmic Reticulum.
Journal Neuron
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.
Volume 109(2)
Pages 299-313.e9
Published 2021-1-20
DOI 10.1016/j.neuron.2020.10.005
PII S0896-6273(20)30773-X
PMID 33157003
PMC PMC7837115
MeSH Animals Autophagy / physiology* Axons / physiology* Endoplasmic Reticulum / physiology* Excitatory Postsynaptic Potentials / physiology Hippocampus / cytology Hippocampus / physiology Mice Mice, 129 Strain Mice, Knockout Mice, Transgenic Neurons / physiology* Organ Culture Techniques Presynaptic Terminals / physiology* Synaptic Transmission / physiology
IF 14.415
Mice RBRC02975