| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2011: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Research Abstract |
It exists as two alternatively spliced isoforms, termed D_2LR and D_2SR. In D_2LR, but not D_2SR, its activation involves in the transactivation of receptor tyrosine kinase (RTK) pathways. We previously demonstrated that D_2SR is predominantly expressed in the plasma membrane, whereas D_2LR is mostly retained in the Golgi apparatus. However, the molecular mechanisms and physiological roles of the intracellular D_2LR remain unclear. Interestingly, persistent ERK activation and D_2R protein synthesis is enhanced by dopamine in..D_2LR transfected cells with PDGFR., but not in D_2SR. The persistent kinase activation and protein synthesis are completely blocked by pertussis-toxin, PDGFR inhibitor and dynamin inhibitor, suggesting the dopamine-induced receptor internalization is involved in the activation of intracellular D_2LR-RTK signaling. In neuron specific Pdgfr. knockout (Pdgfrβ^<-/->) mice, D_2R protein expression significantly decreased in the striatum. Taken together, the dopamine-induced internalization of D_2R and PDGFR. elicits persist activation of ERK pathways, thereby enhancing D_2R protein synthesis.
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