title: EphA signaling promotes actin-based dendritic spine remodeling through slingshot phosphatase.
abstract: Actin cytoskeletal remodeling plays a critical role in transforming the morphology of subcellular structures across various cell types. In the brain, restructuring of dendritic spines through actin cytoskeleletal reorganization is implicated in the regulation of synaptic efficacy and the storage of information in neural circuits. However, the upstream pathways that provoke actin-based spine changes remain only partly understood. Here we show that EphA receptor signaling remodels spines by triggering a sequence of events involving actin filament rearrangement and synapse/spine reorganization. Rapid EphA signaling over minutes activates the actin filament depolymerizing/severing factor cofilin, alters F-actin distribution in spines, and causes transient spine elongation through the phosphatases slingshot 1 (SSH1) and calcineurin/protein phosphatase 2B (PP2B). This early phase of spine extension is followed by synaptic reorganization events that take place over minutes to hours and involve the relocation of pre/postsynaptic components and ultimately spine retraction. Thus, EphA receptors utilize discrete cellular and molecular pathways to promote actin-based structural plasticity of excitatory synapses.
authors.affiliation: Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, The Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, Quebec, Canada.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhou
authors.forename: Emma V
authors.initials: EV
authors.lastname: Jones
authors.forename: Keith K
authors.initials: KK
authors.lastname: Murai
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D019703:Calcineurin / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D051338:Cofilin 1 / Q000235:genetics / Q000378:metabolism; D049229:Dendritic Spines / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism*; D036342:Ephrins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D036081:Receptors, Eph Family / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013131:Spine / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D013569:Synapses / Q000378:metabolism
chemical_list: D000199:Actins; D051338:Cofilin 1; D036342:Ephrins; D036081:Receptors, Eph Family; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases; C484329:SSH1 protein, human; C529575:SSH1 protein, mouse