The Actin Binding Domain of bI-Spectrin Regulates the Morphological and Functional Dynamics of Dendritic Spines

Hdl Handle:
http://hdl.handle.net/10675.2/631
Title:
The Actin Binding Domain of bI-Spectrin Regulates the Morphological and Functional Dynamics of Dendritic Spines
Authors:
Nestor, Michael W.; Cai, Xiang; Stone, Michele R.; Bloch, Robert J.; Thompson, Scott M.
Abstract:
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.
Editors:
Mei, Lin
Citation:
PLoS One. 2011 Jan 31; 6(1):e16197
Issue Date:
31-Jan-2011
URI:
http://hdl.handle.net/10675.2/631
DOI:
10.1371/journal.pone.0016197
PubMed ID:
21297961
PubMed Central ID:
PMC3031527
Type:
Article
ISSN:
1932-6203
Appears in Collections:
Department of Neurology: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorNestor, Michael W.-
dc.contributor.authorCai, Xiang-
dc.contributor.authorStone, Michele R.-
dc.contributor.authorBloch, Robert J.-
dc.contributor.authorThompson, Scott M.-
dc.contributor.editorMei, Lin-
dc.date.accessioned2012-10-26T16:26:55Z-
dc.date.available2012-10-26T16:26:55Z-
dc.date.issued2011-01-31en_US
dc.identifier.citationPLoS One. 2011 Jan 31; 6(1):e16197en_US
dc.identifier.issn1932-6203en_US
dc.identifier.pmid21297961en_US
dc.identifier.doi10.1371/journal.pone.0016197en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/631-
dc.description.abstractActin 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.en_US
dc.rightsNestor et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.subjectResearch Articleen_US
dc.subjectBiologyen_US
dc.subjectAnatomy and Physiologyen_US
dc.subjectElectrophysiologyen_US
dc.subjectBiochemistryen_US
dc.subjectNeurochemistryen_US
dc.subjectSynaptic Plasticityen_US
dc.subjectBiophysicsen_US
dc.subjectCell Motilityen_US
dc.subjectActin Filamentsen_US
dc.subjectNeuroscienceen_US
dc.subjectCellular Neuroscienceen_US
dc.subjectNeuronal Morphologyen_US
dc.subjectMolecular Neuroscienceen_US
dc.subjectSignaling Pathwaysen_US
dc.subjectNeurophysiologyen_US
dc.subjectSynapsesen_US
dc.titleThe Actin Binding Domain of bI-Spectrin Regulates the Morphological and Functional Dynamics of Dendritic Spinesen_US
dc.typeArticleen_US
dc.identifier.pmcidPMC3031527en_US
dc.contributor.corporatenameDepartment of Neurology-
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