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

Daeyoung Oh, Seungnam Han, Jinsoo Seo, Jae Ran Lee, Jeonghoon Choi, John Groffen, Karam Kim, Yi Sul Cho, Han Saem Choi, Hyewon Shin, Jooyeon Woo, Hyejung Won, Soon Kwon Park, Soo Young Kim, Jihoon Jo, Daniel J. Whitcomb, Kwangwook Cho, Hyun Kim, Yong Chul Bae, Nora HeisterkampSe Young Choi, Eunjoon Kim

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69 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)14134-14144
Number of pages11
JournalJournal of Neuroscience
Volume30
Issue number42
DOIs
Publication statusPublished - 2010 Oct 20

ASJC Scopus subject areas

  • Neuroscience(all)

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    Oh, D., Han, S., Seo, J., Lee, J. R., Choi, J., Groffen, J., Kim, K., Cho, Y. S., Choi, H. S., Shin, H., Woo, J., Won, H., Park, S. K., Kim, S. Y., Jo, J., Whitcomb, D. J., Cho, K., Kim, H., Bae, Y. C., ... Kim, E. (2010). Regulation of synaptic Rac1 activity, long-term potentiation maintenance, and learning and memory by BCR and ABR Rac GTPase-activating proteins. Journal of Neuroscience, 30(42), 14134-14144. https://doi.org/10.1523/JNEUROSCI.1711-10.2010