TY - JOUR
T1 - Eps8 controls dendritic spine density and synaptic plasticity through its actin-capping activity
AU - Menna, Elisabetta
AU - Zambetti, Stefania
AU - Morini, Raffaella
AU - Donzelli, Andrea
AU - Disanza, Andrea
AU - Calvigioni, Daniela
AU - Braida, Daniela
AU - Nicolini, Chiara
AU - Orlando, Marta
AU - Fossati, Giuliana
AU - Cristina Regondi, Maria
AU - Pattini, Linda
AU - Frassoni, Carolina
AU - Francolini, Maura
AU - Scita, Giorgio
AU - Sala, Mariaelvina
AU - Fahnestock, Margaret
AU - Matteoli, Michela
PY - 2013/6/12
Y1 - 2013/6/12
N2 - 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.
AB - 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.
KW - actin-capping activity
KW - activity-dependent plasticity
KW - Eps8
KW - learning and memory defects
KW - spine morphogenesis
UR - http://www.scopus.com/inward/record.url?scp=84879462883&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84879462883&partnerID=8YFLogxK
U2 - 10.1038/emboj.2013.107
DO - 10.1038/emboj.2013.107
M3 - Article
C2 - 23685357
AN - SCOPUS:84879462883
VL - 32
SP - 1730
EP - 1744
JO - EMBO Journal
JF - EMBO Journal
SN - 0261-4189
IS - 12
ER -