Regulation of synaptic Rac1 activity, long-term potentiation maintenance, and learning and memory by BCR and ABR Rac GPPase-activating proteins

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Title
Regulation of synaptic Rac1 activity, long-term potentiation maintenance, and learning and memory by BCR and ABR Rac GPPase-activating proteins
Author(s)
D Oh; S Han; J Seo; Jae-Ran Lee; J Choi; J Groffen; K Kim; Y S Cho; H S Choi; H Shin; J Woo; H Won; S K Park; S Y Kim; J Jo; D J Whitcomb; K Cho; H Kim; Y C Bae; N Heisterkamp; S Y Choi; E Kim
Bibliographic Citation
Journal of Neuroscience, vol. 30, no. 42, pp. 14134-14144
Publication Year
2010
Abstract
Rho family small GTPases are important regulators of neuronal development. Defective Rho regulation causes nervous system dysfunctions including mental retardation and Alzheimer's disease. Rac1, a member of the Rho family, regulates dendritic spines and excitatory synapses, but relatively little is known about how synaptic Rac1 is negatively regulated. Breakpoint cluster region (BCR) is a Rac GTPase-activating protein known to form a fusion protein with the c-Abl tyrosine kinase in Philadelphia chromosome-positive chronic myelogenous leukemia. Despite the fact that BCR mRNAs are abundantly expressed in the brain, the neural functions of BCR protein have remained obscure. We report here that BCR and its close relative active BCR-related (ABR) localize at excitatory synapses and directly interact with PSD-95, an abundant postsynaptic scaffolding protein. Mice deficient for BCR or ABR show enhanced basal Rac1 activity but only a small increase in spine density. Importantly, mice lacking BCR or ABR exhibit a marked decrease in the maintenance, but not induction, of long-term potentiation, and show impaired spatial and object recognition memory. These results suggest that BCR and ABR have novel roles in the regulation of synaptic Rac1 signaling, synaptic plasticity, and learning and memory, and that excessive Rac1 activity negatively affects synaptic and cognitive functions.
ISSN
0270-6474
Publisher
Soc Neuroscience
DOI
http://dx.doi.org/10.1523/JNEUROSCI.1711-10.2010
Type
Article
Appears in Collections:
Division of Biomedical Research > Rare Disease Research Center > 1. Journal Articles
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