Eps8 controls dendritic spine density and synaptic plasticity through its actin-capping activity

Elisabetta Menna, Stefania Zambetti, Raffaella Morini, Andrea Donzelli, Andrea Disanza, Daniela Calvigioni, Daniela Braida, Chiara Nicolini, Marta Orlando, Giuliana Fossati, Maria Cristina Regondi, Linda Pattini, Carolina Frassoni, Maura Francolini, Giorgio Scita, Mariaelvina Sala, Margaret Fahnestock, Michela Matteoli

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1730-1744
Number of pages15
JournalEMBO Journal
Volume32
Issue number12
DOIs
Publication statusPublished - Jun 12 2013

Keywords

  • actin-capping activity
  • activity-dependent plasticity
  • Eps8
  • learning and memory defects
  • spine morphogenesis

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)

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