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PMID:17018287
| Citation |
Offenhäuser, N, Castelletti, D, Mapelli, L, Soppo, BE, Regondi, MC, Rossi, P, D'Angelo, E, Frassoni, C, Amadeo, A, Tocchetti, A, Pozzi, B, Disanza, A, Guarnieri, D, Betsholtz, C, Scita, G, Heberlein, U and Di Fiore, PP (2006) Increased ethanol resistance and consumption in Eps8 knockout mice correlates with altered actin dynamics. Cell 127:213-26 |
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| 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. |
| Links |
PubMed Online version:10.1016/j.cell.2006.09.011 |
| Keywords |
Actins/metabolism; Adaptor Proteins, Signal Transducing/genetics; Adaptor Proteins, Signal Transducing/metabolism; Alcohol Drinking; Animals; Behavior, Animal/drug effects; Behavior, Animal/physiology; Cells, Cultured; Central Nervous System Depressants/pharmacology; Cerebellum/cytology; Cytoskeletal Proteins/genetics; Cytoskeletal Proteins/metabolism; Cytoskeleton/drug effects; Cytoskeleton/metabolism; Ethanol/pharmacology; Female; Humans; Male; Mice; Mice, Knockout; Neurons/cytology; Neurons/drug effects; Neurons/metabolism; Receptors, N-Methyl-D-Aspartate/metabolism; Recombinant Proteins/genetics; Recombinant Proteins/metabolism; Signal Transduction/physiology |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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