title: Eps8 controls dendritic spine density and synaptic plasticity through its actin-capping activity.
abstract: Actin-based remodelling underlies spine structural changes occurring during synaptic plasticity, the process that constantly reshapes the circuitry of the adult brain in response to external stimuli, leading to learning and memory formation. A positive correlation exists between spine shape and synaptic strength and, consistently, abnormalities in spine number and morphology have been described in a number of neurological disorders. In the present study, we demonstrate that the actin-regulating protein, Eps8, is recruited to the spine head during chemically induced long-term potentiation in culture and that inhibition of its actin-capping activity impairs spine enlargement and plasticity. Accordingly, mice lacking Eps8 display immature spines, which are unable to undergo potentiation, and are impaired in cognitive functions. Additionally, we found that reduction in the levels of Eps8 occurs in brains of patients affected by autism compared to controls. Our data reveal the key role of Eps8 actin-capping activity in spine morphogenesis and plasticity and indicate that reductions in actin-capping proteins may characterize forms of intellectual disabilities associated with spine defects.
authors.affiliation: CNR Institute of Neuroscience, Milano, Italy. e.menna@in.cnr.it
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Menna
authors.forename: Stefania
authors.initials: S
authors.lastname: Zambetti
authors.forename: Raffaella
authors.initials: R
authors.lastname: Morini
authors.forename: Andrea
authors.initials: A
authors.lastname: Donzelli
authors.forename: Andrea
authors.initials: A
authors.lastname: Disanza
authors.forename: Daniela
authors.initials: D
authors.lastname: Calvigioni
authors.forename: Daniela
authors.initials: D
authors.lastname: Braida
authors.forename: Chiara
authors.initials: C
authors.lastname: Nicolini
authors.forename: Marta
authors.initials: M
authors.lastname: Orlando
authors.forename: Giuliana
authors.initials: G
authors.lastname: Fossati
authors.forename: Maria
authors.initials: M
authors.lastname: Cristina Regondi
authors.forename: Linda
authors.initials: L
authors.lastname: Pattini
authors.forename: Carolina
authors.initials: C
authors.lastname: Frassoni
authors.forename: Maura
authors.initials: M
authors.lastname: Francolini
authors.forename: Giorgio
authors.identifier: 0000000179841889
authors.initials: G
authors.lastname: Scita
authors.forename: Mariaelvina
authors.initials: M
authors.lastname: Sala
authors.forename: Margaret
authors.initials: M
authors.lastname: Fahnestock
authors.forename: Michela
authors.initials: M
authors.lastname: Matteoli
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001321:Autistic Disorder / Q000235:genetics / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D003071:Cognition / Q000502:physiology; D049229:Dendritic Spines / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017774:Long-Term Potentiation / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000235:genetics / Q000378:metabolism*
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; C083430:Eps8 protein, mouse; D009419:Nerve Tissue Proteins