2012 Fiscal Year Final Research Report
Molecular mechanisms of the intracellular dopamine D2 receptor
| Project/Area Number |
23790072
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Biological pharmacy
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| Research Institution | Tohoku University |
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Principal Investigator |
SHIODA Norifumi 東北大学, 大学院・薬学研究科, 助教 (00374950)
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| Project Period (FY) |
2011 – 2012
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| Keywords | ドパミン D2 受容体 / 細胞内小器官 / シグナル伝達機構 |
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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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[Journal Article] Reduced expressionof the ATRX gene, a chromatin-remodeling factor, causes hippocampal dysfunction in mice2011
Author(s)
Nogami T, Beppu H, Tokoro T, Moriguchi S, Shioda N, Fukunaga K, Ohtsuka T, Ishii Y, Sasahara M, Shimada Y, Nishijo H, Li E, Kitajima I
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Journal Title
Hippocampus
Volume: 21
Pages: 678-687
Peer Reviewed
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