PT  - JOURNAL ARTICLE
AU  - Mohamad Bouhamdan
AU  - Hai-Dun Yan
AU  - Xiu-Hua Yan
AU  - Michael J. Bannon
AU  - Rodrigo Andrade
TI  - Brain-Specific Regulator of G-Protein Signaling 9-2 Selectively Interacts with α-Actinin-2 to Regulate Calcium-Dependent Inactivation of NMDA Receptors
AID  - 10.1523/JNEUROSCI.4083-05.2006
DP  - 2006 Mar 01
TA  - The Journal of Neuroscience
PG  - 2522--2530
VI  - 26
IP  - 9
4099  - http://www.jneurosci.org/content/26/9/2522.short
4100  - http://www.jneurosci.org/content/26/9/2522.full
SO  - J. Neurosci.2006 Mar 01; 26
AB  - Regulator of G-protein signaling 9-1 (RGS9-1) and RGS9-2 are highly related RGS proteins with distinctive C termini arising from alternative splicing of RGS9 gene transcripts. RGS9-1 is expressed in photoreceptors where it functions as a regulator of transducin. In contrast, RGS9-2 is abundantly expressed in the brain, especially in basal ganglia, where its specific function remains poorly understood. To gain insight into the function of RGS9-2, we screened a human cDNA library for potential interacting proteins. This screen identified a strong interaction between RGS9-2 and α-actinin-2, suggesting a possible functional relationship between these proteins. Consistent with this idea, RGS9-2 and α-actinin-2 coimmunoprecipitated after coexpression in human embryonic kidney 293 (HEK-293) cells. Furthermore, endogenous RGS9-2 and α-actinin-2 could also be coimmunoprecipitated from extracts of rat striatum, an area highly enriched in both these proteins. These results supported the idea that RGS9-2 and α-actinin-2 could act in concert in central neurons. Like α-actinin-2, RGS9-2 coimmunoprecipitated NMDA receptors from striatal extracts, suggesting an interaction between RGS9-2, α-actinin-2, and NMDA receptors. Previous studies have shown that α-actinin mediates calcium-dependent inactivation of NMDA receptors. In HEK-293 cells expressing NMDA receptors, expression of RGS9-2 significantly modulated this form of NMDA receptor inactivation. Furthermore, this modulation showed remarkable preference for NMDA receptor inactivation mediated by α-actinin-2. Using a series of deletion constructs, we localized this effect to the RGS domain of the protein. These results identify an unexpected functional interaction between RGS9-2 and α-actinin-2 and suggest a potential novel role for RGS9-2 in the regulation of NMDA receptor function.