EndoA/Endophilin-A creates docking stations for autophagic proteins at synapses. Issue 5 (4th May 2017)

• Record Type: Journal Article
• Authors: Soukup, Sandra-Fausia; Verstreken, Patrik
• Is Part Of: Autophagy. Volume 13:Issue 5(2017)
• Page Start: 971
• Page End: 972
• Publication Date: 2017-05-04
• Subjects: ATG3 -- autophagic docking stations -- autophagy -- Drosophila -- Endophilin-A -- LRRK2 -- membrane curvature -- neurodegeneration -- Parkinson disease -- synapses; Autophagic vacuoles -- Periodicals; Apoptosis -- Periodicals; Cell death -- Periodicals; Lysosomes -- Periodicals; Degeneration (Pathology) -- Periodicals; Autophagy -- Periodicals; Cell Death -- Periodicals; Lysosomes -- Periodicals; Periodicals; 571.936
• DOI: 10.1080/15548627.2017.1286440
• Languages: English
• ISSNs: 1554-8627

Abstract

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.