PT  - JOURNAL ARTICLE
AU  - Drew D. Kiraly
AU  - Fouad Lemtiri-Chlieh
AU  - Eric S. Levine
AU  - Richard E. Mains
AU  - Betty A. Eipper
TI  - Kalirin Binds the NR2B Subunit of the NMDA Receptor, Altering Its Synaptic Localization and Function
AID  - 10.1523/JNEUROSCI.3143-11.2011
DP  - 2011 Aug 31
TA  - The Journal of Neuroscience
PG  - 12554--12565
VI  - 31
IP  - 35
4099  - http://www.jneurosci.org/content/31/35/12554.short
4100  - http://www.jneurosci.org/content/31/35/12554.full
SO  - J. Neurosci.2011 Aug 31; 31
AB  - The ability of dendritic spines to change size and shape rapidly is critical in modulating synaptic strength; these morphological changes are dependent upon rearrangements of the actin cytoskeleton. Kalirin-7 (Kal7), a Rho guanine nucleotide exchange factor localized to the postsynaptic density (PSD), modulates dendritic spine morphology in vitro and in vivo. Kal7 activates Rac and interacts with several PSD proteins, including PSD-95, DISC-1, AF-6, and Arf6. Mice genetically lacking Kal7 (Kal7KO) exhibit deficient hippocampal long-term potentiation (LTP) as well as behavioral abnormalities in models of addiction and learning. Purified PSDs from Kal7KO mice contain diminished levels of NR2B, an NMDA receptor subunit that plays a critical role in LTP induction. Here we demonstrate that Kal7KO animals have decreased levels of NR2B-dependent NMDA receptor currents in cortical pyramidal neurons as well as a specific deficit in cell surface expression of NR2B. Additionally, we demonstrate that the genotypic differences in conditioned place preference and passive avoidance learning seen in Kal7KO mice are abrogated when animals are treated with an NR2B-specific antagonist during conditioning. Finally, we identify a stable interaction between the pleckstrin homology domain of Kal7 and the juxtamembrane region of NR2B preceding its cytosolic C-terminal domain. Binding of NR2B to a protein that modulates the actin cytoskeleton is important, as NMDA receptors require actin integrity for synaptic localization and function. These studies demonstrate a novel and functionally important interaction between the NR2B subunit of the NMDA receptor and Kalirin, proteins known to be essential for normal synaptic plasticity.