title: Liprin-α2 promotes the presynaptic recruitment and turnover of RIM1/CASK to facilitate synaptic transmission.
abstract: The presynaptic active zone mediates synaptic vesicle exocytosis, and modulation of its molecular composition is important for many types of synaptic plasticity. Here, we identify synaptic scaffold protein liprin-α2 as a key organizer in this process. We show that liprin-α2 levels were regulated by synaptic activity and the ubiquitin-proteasome system. Furthermore, liprin-α2 organized presynaptic ultrastructure and controlled synaptic output by regulating synaptic vesicle pool size. The presence of liprin-α2 at presynaptic sites did not depend on other active zone scaffolding proteins but was critical for recruitment of several components of the release machinery, including RIM1 and CASK. Fluorescence recovery after photobleaching showed that depletion of liprin-α2 resulted in reduced turnover of RIM1 and CASK at presynaptic terminals, suggesting that liprin-α2 promotes dynamic scaffolding for molecular complexes that facilitate synaptic vesicle release. Therefore, liprin-α2 plays an important role in maintaining active zone dynamics to modulate synaptic efficacy in response to changes in network activity.
authors.affiliation: Department of Neuroscience, Erasmus Medical Center, 3015GE Rotterdam, Netherlands.
authors.forename: Samantha A
authors.initials: SA
authors.lastname: Spangler
authors.forename: Sabine K
authors.initials: SK
authors.lastname: Schmitz
authors.forename: Josta T
authors.initials: JT
authors.lastname: Kevenaar
authors.forename: Esther
authors.initials: E
authors.lastname: de Graaff
authors.forename: Heidi
authors.initials: H
authors.lastname: de Wit
authors.forename: Jeroen
authors.initials: J
authors.lastname: Demmers
authors.forename: Ruud F
authors.initials: RF
authors.lastname: Toonen
authors.forename: Casper C
authors.initials: CC
authors.lastname: Hoogenraad
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051528:Guanylate Kinases / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008854:Microscopy, Electron; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D010641:Phenotype; D017729:Presynaptic Terminals / Q000378:metabolism / Q000648:ultrastructure; D061251:Primary Cell Culture; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D051381:Rats; D009435:Synaptic Transmission / Q000502:physiology*; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D008565:Membrane Proteins; C582811:Ppfia2 protein, rat; C491489:Rims1 protein, rat; D025801:Ubiquitin; C106868:CASK kinases; D051528:Guanylate Kinases; D046988:Proteasome Endopeptidase Complex; D019204:GTP-Binding Proteins