Qu Zhongwei, Wang Yuqing, Li Xia, Wu Lin, Wang Yizheng
Laboratory of Neural Signal Transduction, Institute of Neuroscience, Chinese Academy of Sciences, Shanghai, China.
The Graduate School, University of Chinese Academy of Sciences, Beijing, China.
J Neurochem. 2017 Nov;143(3):282-293. doi: 10.1111/jnc.14215. Epub 2017 Oct 13.
The expression of transient receptor potential canonical 6 (TRPC6) in central nervous system (CNS) is important for neuronal functions and certain neural disorders. However, the regulatory mechanism of TRPC6 expression in neurons is still obscure. In this study, we show that TRPC6 expression in the primary cultured cortical neurons is bidirectionally regulated by glutamate. Activation of NR2A-containing NMDARs induces TRPC6 transcription through a calcineurin-dependent pathway. In contrast, activation of NR2B-containing NMDARs causes TRPC6 degradation through calpain. Thus, TRPC6 expression in neurons is regulated by glutamate in a bidirectional manner that is dependent on NR2A and NR2B.
瞬时受体电位香草酸亚型6（TRPC6）在中枢神经系统（CNS）中的表达对神经元功能及某些神经疾病至关重要。然而，神经元中TRPC6表达的调控机制仍不清楚。在本研究中，我们发现原代培养的皮层神经元中TRPC6的表达受谷氨酸双向调控。含NR2A的NMDARs激活通过钙调神经磷酸酶依赖途径诱导TRPC6转录。相反，含NR2B的NMDARs激活通过钙蛋白酶导致TRPC6降解。因此，神经元中TRPC6的表达由谷氨酸以依赖于NR2A和NR2B的双向方式调控。
