Browsing Department of Neurology: Faculty Research and Presentations by Authors
The Actin Binding Domain of bI-Spectrin Regulates the Morphological and Functional Dynamics of Dendritic SpinesNestor, Michael W.; Cai, Xiang; Stone, Michele R.; Bloch, Robert J.; Thompson, Scott M.; Mei, Lin; Department of Neurology (2011-01-31)Actin microfilaments regulate the size, shape and mobility of dendritic spines and are in turn regulated by actin binding proteins and small GTPases. The bI isoform of spectrin, a protein that links the actin cytoskeleton to membrane proteins, is present in spines. To understand its function, we expressed its actin-binding domain (ABD) in CA1 pyramidal neurons in hippocampal slice cultures. The ABD of bI-spectrin bundled actin in principal dendrites and was concentrated in dendritic spines, where it significantly increased the size of the spine head. These effects were not observed after expression of homologous ABDs of utrophin, dystrophin, and a-actinin. Treatment of slice cultures with latrunculin-B significantly decreased spine head size and decreased actin-GFP fluorescence in cells expressing the ABD of a-actinin, but not the ABD of bI-spectrin, suggesting that its presence inhibits actin depolymerization. We also observed an increase in the area of GFPtagged PSD-95 in the spine head and an increase in the amplitude of mEPSCs at spines expressing the ABD of bI-spectrin. The effects of the bI-spectrin ABD on spine size and mEPSC amplitude were mimicked by expressing wild-type Rac3, a small GTPase that co-immunoprecipitates specifically with bI-spectrin in extracts of cultured cortical neurons. Spine size was normal in cells co-expressing a dominant negative Rac3 construct with the bI-spectrin ABD. We suggest that bI-spectrin is a synaptic protein that can modulate both the morphological and functional dynamics of dendritic spines, perhaps via interaction with actin and Rac3.