Journal
NEUROPHARMACOLOGY
Volume 56, Issue 1, Pages 73-80Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2008.06.055
Keywords
Rho GTPase; PAK1 knockout mice; Actin cytoskeleton; Cofilin; Hippocampal long-term potentiation
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Funding
- Canadian Institutes of Health Research [CIHR MOP-42396]
- Ontario Mental Health Foundation
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The Rho family small GTPases are critically involved in the regulation of spine and synaptic properties, but the underlying mechanisms are poorly defined. We took genetic approaches to create and analyze knockout mice deficient in the expression of the protein kinase PAKI that is directly associated with and activated by the Rho GTPases. We demonstrated that while these knockout mice were normal in both basal and presynaptic function, they were selectively impaired in long-term potentiation (LTP) at hippocampal CA1 synapses. Consistent with the electrophysiological deficits, the PAKI knockout mice showed changes in the actin cytoskeleton and the actin binding protein cofilin. These results indicate that PAK1 is critical in hippocampal synaptic plasticity via regulating cofilin activity and the actin cytoskeleton. (C) 2008 Elsevier Ltd. All rights reserved.
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