Neurons rely on autophagy for the removal of defective proteins or organelles to maintain synaptic neurotransmission and counteract neurodegeneration, yet the physiological substrates of neuronal autophagy have remained largely elusive. We use knockout mice conditionally lacking the essential autophagy protein ATG5 to demonstrate that loss of neuronal autophagy causes selective accumulation of tubular endoplasmic reticulum (ER) in axons and an increase in excitatory neurotransmission. Calcium imaging experiments show that ATG5 KO neurons suffer from altered calcium homeostasis and an increased ER-calcium release through ER-localized ryanodine receptors (RYR) that accumulate in autophagy-deficient axons. We propose a model where neuronal autophagy controls axonal ER calcium stores to regulate release probability and neuronal excitability.
Organizer
Dick Jaarsma
d.jaarsma@erasmusmc.nl