|Budget Amount *help
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2010: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
We examined molecular mechanisms and in vivo functions of GRIN3.In this study, we revealed that GRIN3 modulated both signal transduction and amounts of dopamine D2 receptor. GRIN3 was able to bind to not only Galpha(o) but also GRK family. Especially, GRIN3 binding with GRK6 was greatly enhanced in a manner of Galpha(o) binding to GRIN3.Probably, by this mechanism, GRIN3 trapped the crucial region of GRK2 and GRK6 for desensitization of D2 receptor, and potentiated G protein signaling. Thus, GRIN3 seems to be inhibitor of GRK family, at least GRK2 and GRK6.Finally, we observed that GRIN3 KO mice showed less locomotor activity, increased anxiety, and less sensitivity for dopamine transporter inhibitor, GBR12909.