title: EndoA/Endophilin-A creates docking stations for autophagic proteins at synapses.
abstract: Synapses are very specialized compartments with high metabolic demand to maintain neurotransmission, an essential step for basic brain function. Neurons are post-mitotic and synapses need to stay functional over time-sometimes over decades. Given that synapses are often at a long distance from the cell body, they must use local mechanisms to regulate protein quality control. We show that macroautophagy/autophagy is one of these local processes and found that it is under strict control of the synapse-enriched protein EndoA/Endophilin-A, previously only implicated in endocytosis. Metabolic and neuronal stimulation induce synaptic autophagy and phosphorylation of EndoA by the Parkinson disease kinase Lrrk/LRRK2 is essential to promote the process. EndoA induces membrane curvature in vitro, and, mechanistically, phosphorylated EndoA creates curved membrane-protein docking sites that are capable of recruiting Atg3. Our work reveals a synapse-enriched branch of autophagy under the control of EndoA that may be deregulated in Parkinson disease.
authors.affiliation: a VIB Center for Brain & Disease Research , Leuven , Belgium.|b KU Leuven, Department of Neurosciences , Leuven Institute for Neurodegenerative Disease (LIND) , Leuven , Belgium.
authors.forename: Sandra-Fausia
authors.initials: SF
authors.lastname: Soukup
authors.affiliation: a VIB Center for Brain & Disease Research , Leuven , Belgium.|b KU Leuven, Department of Neurosciences , Leuven Institute for Neurodegenerative Disease (LIND) , Leuven , Belgium.
authors.forename: Patrik
authors.initials: P
authors.lastname: Verstreken
mesh_terms: D000818:Animals; D006801:Humans; D000217:Acyltransferases / Q000378:metabolism; D001343:Autophagy / Q000502:physiology; D029721:Drosophila Proteins / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D013569:Synapses / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D000217:Acyltransferases; D029721:Drosophila Proteins; C456023:endophilin A, Drosophila
keywords: ATG3; Drosophila; Endophilin-A; LRRK2; Parkinson disease; autophagic docking stations; autophagy; membrane curvature; neurodegeneration; synapses