Increased Ethanol Resistance and Consumption in Eps8 Knockout Mice Correlates with Altered Actin Dynamics

Nina Offenhäuser, Daniela Castelletti, Lisa Mapelli, Blanche Ekalle Soppo, Maria Cristina Regondi, Paola Rossi, Egidio D'Angelo, Carolina Frassoni, Alida Amadeo, Arianna Tocchetti, Benedetta Pozzi, Andrea Disanza, Douglas Guarnieri, Christer Betsholtz, Giorgio Scita, Ulrike Heberlein, Pier Paolo Di Fiore

Research output: Contribution to journalArticle

Abstract

Dynamic modulation of the actin cytoskeleton is critical for synaptic plasticity, abnormalities of which are thought to contribute to mental illness and addiction. Here we report that mice lacking Eps8, a regulator of actin dynamics, are resistant to some acute intoxicating effects of ethanol and show increased ethanol consumption. In the brain, the N-methyl-D-aspartate (NMDA) receptor is a major target of ethanol. We show that Eps8 is localized to postsynaptic structures and is part of the NMDA receptor complex. Moreover, in Eps8 null mice, NMDA receptor currents and their sensitivity to inhibition by ethanol are abnormal. In addition, Eps8 null neurons are resistant to the actin-remodeling activities of NMDA and ethanol. We propose that proper regulation of the actin cytoskeleton is a key determinant of cellular and behavioral responses to ethanol.

Original languageEnglish
Pages (from-to)213-226
Number of pages14
JournalCell
Volume127
Issue number1
DOIs
Publication statusPublished - Oct 6 2006

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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    Offenhäuser, N., Castelletti, D., Mapelli, L., Soppo, B. E., Regondi, M. C., Rossi, P., D'Angelo, E., Frassoni, C., Amadeo, A., Tocchetti, A., Pozzi, B., Disanza, A., Guarnieri, D., Betsholtz, C., Scita, G., Heberlein, U., & Di Fiore, PP. (2006). Increased Ethanol Resistance and Consumption in Eps8 Knockout Mice Correlates with Altered Actin Dynamics. Cell, 127(1), 213-226. https://doi.org/10.1016/j.cell.2006.09.011