A critical role of Rho-kinase ROCK2 in the regulation of spine and synaptic function

The actin cytoskeleton is critically involved in the regulation of the dendritic spine and synaptic properties, but the molecular mechanisms underlying actin dynamics in neurons are poorly defined. We took genetic approaches to create and analyze knockout mice specifically lacking ROCK2, a protein k...

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Bibliographic Details
Published in:Neuropharmacology 2009-01, Vol.56 (1), p.81-89
Main Authors: Zhou, Zikai, Meng, Yanghong, Asrar, Suhail, Todorovski, Zarko, Jia, Zhengping
Format: Article
Language:English
Subjects:
Actin Depolymerizing Factors - metabolism
Actin filaments
Animals
Animals, Newborn
Biophysics
Cells, Cultured
Dendritic spine
Dendritic Spines - metabolism
Dendritic Spines - physiology
Dendritic Spines - ultrastructure
Electric Stimulation
Excitatory Amino Acid Agonists - pharmacology
Excitatory Postsynaptic Potentials - genetics
Gene Expression Regulation - drug effects
Gene Expression Regulation - genetics
Glycine - pharmacology
Glycine Agents - pharmacology
Hippocampal long-term potentiation
Hippocampus - cytology
In Vitro Techniques
Long-Term Potentiation - genetics
Mice
Mice, Knockout
Microscopy, Electron, Transmission - methods
N-Methylaspartate - pharmacology
Neurons - drug effects
Neurons - ultrastructure
Patch-Clamp Techniques
Phalloidine - metabolism
Rho GTPase
rho-Associated Kinases - deficiency
rho-Associated Kinases - physiology
ROCK2 knockout mice
Synapses - physiology
Synapses - ultrastructure
Synapsins - metabolism
Vesicular Glutamate Transport Protein 1 - metabolism
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Summary:The actin cytoskeleton is critically involved in the regulation of the dendritic spine and synaptic properties, but the molecular mechanisms underlying actin dynamics in neurons are poorly defined. We took genetic approaches to create and analyze knockout mice specifically lacking ROCK2, a protein kinase that directly interacts with and is activated by the Rho GTPases, the central mediator of actin reorganization. We demonstrated that while these knockout mice were normal in gross brain anatomy, they were impaired in both basal synaptic transmission and hippocampal long-term potentiation (LTP). Consistent with the electrophysiological deficits, the ROCK2 knockout neurons showed deficits in spine properties, synapse density, the actin cytoskeleton, and the actin-binding protein cofilin. These results indicate that ROCK2/cofilin signaling is critical in the regulation of neuronal actin, spine morphology and synaptic function.
ISSN:0028-3908
1873-7064
DOI:10.1016/j.neuropharm.2008.07.031