TRPC6 expression in neurons is differentially regulated by NR2A‐ and NR2B‐containing NMDA receptors. Issue 3 (13th October 2017)

• Record Type: Journal Article
• Authors: Qu, Zhongwei; Wang, Yuqing; Li, Xia; Wu, Lin; Wang, Yizheng
• Is Part Of: Journal of neurochemistry. Volume 143:Issue 3(2017)
• Page Start: 282
• Page End: 293
• Publication Date: 2017-10-13
• Subjects: calcineurin -- calpain -- NMDA receptors -- TRPC6; Neurochemistry -- Periodicals; 616.8042
• DOI: 10.1111/jnc.14215
• Languages: English
• ISSNs: 0022-3042

Abstract

Abstract: 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. Abstract : The regulatory mechanism of TRPC6 expression in neurons is still obscure. We proposed that activation of NR2A‐containing NMDARs stimulates the calcineurin pathway to increase transcription of TRPC6, leading to consequent up‐regulation of TRPC6 protein and its activities. Glutamate also activates NR2B‐containing NMDARs, leading to calpain activation and TRPC6 protein degradation.