Analysis of novel intracellular signal transduction mechanism of metabotropic glutamate receptor.

代谢性谷氨酸受体(MGluRs)在学习和记忆形成等高级大脑功能中起着至关重要的作用。本研究的目的是确定mGluR的新的信号转导机制，并阐明mGluR介导的突触功能调节的全貌。对mGluR1a的特征C末端胞内区的分析揭示了控制受体分子在胞内定位的新的蛋白质区域。此外，利用新开发的酵母三杂交系统对文库进行筛选，成功地鉴定了新的mGluR相互作用分子。这些结果可能加深对中枢神经系统突触调节的分子理解，新发现的分子可能成为治疗神经精神疾病药物开发的候选分子。

Metabotropic glutamate receptors (mGluRs) play crucial roles in higher brain functions such as learning and memory formation. The purpose of this researchproject is to identify novel signal transduction mechanisms of mGluRs and to elucidate the whole picture of mGluR-mediated regulation of synaptic function. Analysis of characteristic long C-terminal intracellular domain of mGluR1a revealed novel protein regions that controls intracellular localization of receptor molecules. Furthermore, screening of cDNA library using newly-developed yeast three-hybrid system successfully identify novel mGluR-interacting molecules. These results may improve the molecular understanding of synaptic regulation of central nervous system, and newly-identified molecules may become the candidate of drug development for neuropsychiatric diseases.