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 LRRK2G2019S. 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. [Display omitted] •Endophilin-B regulates autophagy downstream of Endophilin-A and LRRK2.•Endophilin-B is necessary for autophagy during synapse development•Endophilin-B null mutant animals show supernumerary photoreceptor synapses.•Endophilin-B protects photoreceptors and dopamine neurons from neurodegeneration.