Endophilin-B regulates autophagy during synapse development and neurodegeneration

Synapses are critical for neuronal communication and brain function. To maintain neuronal homeostasis, synapses rely on autophagy. Autophagic alterations cause neurodegeneration and synaptic dysfunction is a feature in neurodegenerative diseases. In Parkinson's disease (PD), where the loss of synapses precedes dopaminergic neuron loss, various PD-causative proteins are involved in the regulation of autophagy. So far only a few factors regulating autophagy at the synapse have been identified and the molecular mechanisms underlying autophagy at the synapse is only partially understood. Here, we describe Endophilin-B (EndoB) as a novel player in the regulation of synaptic autophagy in health and disease. We demonstrate that EndoB is required for autophagosome biogenesis at the synapse, whereas the loss of EndoB blocks the autophagy induction promoted by the PD mutation LRRK2(G2019S). We show that EndoB is required to prevent neuronal loss. Moreover, loss of EndoB in the Drosophila visual system leads to an increase in synaptic contacts between photoreceptor terminals and their post-synaptic synapses. These data confirm the role of autophagy in synaptic contact formation and neuronal survival.

Automated summary

Synapses are essential for neuronal communication and brain function, and autophagy plays a critical role in maintaining synaptic homeostasis. Synaptic dysfunction is a characteristic feature of neurodegenerative diseases, including Parkinson's disease. This study identifies Endophilin-B (EndoB) as a novel regulator of synaptic autophagy in health and disease. The findings demonstrate that EndoB is required for autophagosome biogenesis at the synapse and loss of EndoB impairs autophagy induction promoted by the PD-associated mutation LRRK2(G2019S). Furthermore, EndoB is necessary for preventing neuronal loss and it plays a role in synaptic contact formation.