PT  - JOURNAL ARTICLE
AU  - Daeyoung Oh
AU  - Seungnam Han
AU  - Jinsoo Seo
AU  - Jae-Ran Lee
AU  - Jeonghoon Choi
AU  - John Groffen
AU  - Karam Kim
AU  - Yi Sul Cho
AU  - Han-Saem Choi
AU  - Hyewon Shin
AU  - Jooyeon Woo
AU  - Hyejung Won
AU  - Soon Kwon Park
AU  - Soo-Young Kim
AU  - Jihoon Jo
AU  - Daniel J. Whitcomb
AU  - Kwangwook Cho
AU  - Hyun Kim
AU  - Yong Chul Bae
AU  - Nora Heisterkamp
AU  - Se-Young Choi
AU  - Eunjoon Kim
TI  - Regulation of Synaptic Rac1 Activity, Long-Term Potentiation Maintenance, and Learning and Memory by BCR and ABR Rac GTPase-Activating Proteins
AID  - 10.1523/JNEUROSCI.1711-10.2010
DP  - 2010 Oct 20
TA  - The Journal of Neuroscience
PG  - 14134--14144
VI  - 30
IP  - 42
4099  - http://www.jneurosci.org/content/30/42/14134.short
4100  - http://www.jneurosci.org/content/30/42/14134.full
SO  - J. Neurosci.2010 Oct 20; 30
AB  - 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.