Niu Long-Gang, Liu Ping, Wang Zhao-Wen, Chen Bojun
Department of Neuroscience, University of Connecticut Health Center, Farmington, United States.
Elife. 2020 Apr 21;9:e53986. doi: 10.7554/eLife.53986.
Slo2 potassium channels play important roles in neuronal function, and their mutations in humans may cause epilepsies and cognitive defects. However, it is largely unknown how Slo2 is regulated by other proteins. Here we show that the function of Slo2 (SLO-2) depends on , a gene important to RNA editing. ADR-1 promotes SLO-2 function not by editing the transcripts of but those of , which encodes an orthologue of mammalian SCYL1. Transcripts of are greatly decreased in mutants due to deficient RNA editing at a single adenosine in their 3'-UTR. SCYL-1 physically interacts with SLO-2 in neurons. Single-channel open probability () of neuronal SLO-2 is ~50% lower in knockout mutant than wild type. Moreover, human Slo2.2/Slack is doubled by SCYL1 in a heterologous expression system. These results suggest that SCYL-1/SCYL1 is an evolutionarily conserved regulator of Slo2 channels.
Slo2钾通道在神经元功能中发挥重要作用，其在人类中的突变可能导致癫痫和认知缺陷。然而，Slo2如何被其他蛋白质调节在很大程度上尚不清楚。在这里，我们表明Slo2（SLO-2）的功能依赖于ADR-1，一个对RNA编辑很重要的基因。ADR-1促进SLO-2功能不是通过编辑ADR-1的转录本，而是通过编辑scyl-1的转录本，scyl-1编码哺乳动物SCYL1的一个直系同源物。由于其3'-UTR中单个腺苷的RNA编辑缺陷，scyl-1的转录本在adr-1突变体中大大减少。SCYL-1在神经元中与SLO-2发生物理相互作用。在adr-1基因敲除突变体中，神经元SLO-2的单通道开放概率（Po）比野生型低约50%。此外，在异源表达系统中，人Slo2.2/Slack的活性被SCYL1提高了一倍。这些结果表明，SCYL-1/SCYL1是Slo2通道在进化上保守的调节因子。
