Studies on the signal transduction mechanisms regulated by heterodimer formation of GPCR

2016 Fiscal Year Final Research Report

• Project/Area Number: 26870292
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry; Functional biochemistry
• Research Institution: Kyoto University
• Principal Investigator: Kasai Rinshi 京都大学, ウイルス・再生医科学研究所, 助教 (20447949)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 生物物理 / １分子計測 / 生理学 / シグナル伝達 / バイオテクノロジー / G蛋白質共役型受容体 / ドーパミン受容体 / ダイマー形成

Outline of Final Research Achievements

G-protein coupled receptor (GPCR) have been thought to form a heterodimer to modulate their functions. However, their existence and functions are not well studied yet. By employing dual color single molecule observation technique, we found that two GPCRs, Dopamine D1R and D2R form a quite transient dimer on the plasma membrane with the lifetime of 30 ms under the physiological conditions. Upon the addition of dopamine, the transient dimer formation was still observed with around seven times longer lifetime, whereas the dimer-monomer equilibrium constant increased by a factor of around 2.5, meaning the decrease of the density of the transient dimers. Therefore, it was suggested that both quantitative and qualitative changes of heterodimers are necessary for a downstream signal production.

Free Research Field

生物物理学