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Interactions between drebrin and Ras regulate dendritic spine plasticity
Author(s) -
Biou Virginie,
Brinkhaus Heike,
Malenka Robert C.,
Matus Andrew
Publication year - 2008
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2008.06269.x
Subject(s) - dendritic spine , dendritic filopodia , filopodia , microbiology and biotechnology , spine (molecular biology) , actin , synaptic plasticity , biology , hippocampal formation , chemistry , neuroscience , receptor , biochemistry
Dendritic spines are major sites of morphological plasticity in the CNS, but the molecular mechanisms that regulate their dynamics remain poorly understood. Here we show that the association of drebrin with actin filaments plays a major role in regulating dendritic spine stability and plasticity. Overexpressing drebrin or the internal actin‐binding site of drebrin in rat hippocampal neurons destabilized mature dendritic spines so that they lost synaptic contacts and came to resemble immature dendritic filopodia. Drebrin‐induced spine destabilization was dependent on Ras activation: expression of constitutively active Ras destabilized spine morphology whereas drebrin‐induced spine destabilization was rescued by co‐expressing dominant negative Ras. Conversely, RNAi‐mediated drebrin knockdown prevented Ras‐induced destabilization and promoted spine maturation in developing neurons. Together these data demonstrate a novel mechanism in which the balance between stability and plasticity in dendritic spines depends on binding of drebrin to actin filaments in a manner that is regulated by Ras.