Oh Kelly H, Haney James J, Wang Xiaohong, Chuang Chiou-Fen, Richmond Janet E, Kim Hongkyun
Department of Cell Biology and Anatomy, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, United States.
Department of Biology, Lake Forest College, Lake Forest, United States.
Elife. 2017 Feb 7;6:e24733. doi: 10.7554/eLife.24733.
Voltage- and calcium-dependent BK channels regulate calcium-dependent cellular events such as neurotransmitter release by limiting calcium influx. Their plasma membrane abundance is an important factor in determining BK current and thus regulation of calcium-dependent events. In , we show that ERG-28, an endoplasmic reticulum (ER) membrane protein, promotes the trafficking of SLO-1 BK channels from the ER to the plasma membrane by shielding them from premature degradation. In the absence of ERG-28, SLO-1 channels undergo aspartic protease DDI-1-dependent degradation, resulting in markedly reduced expression at presynaptic terminals. Loss of suppressed phenotypic defects of gain-of-function mutants in locomotion, neurotransmitter release, and calcium-mediated asymmetric differentiation of the AWC olfactory neuron pair, and conferred significant ethanol-resistant locomotory behavior, resembling loss-of-function mutants, albeit to a lesser extent. Our study thus indicates that the control of BK channel trafficking is a critical regulatory mechanism for synaptic transmission and neural function.
电压和钙依赖性大电导钙激活钾通道（BK通道）通过限制钙内流来调节钙依赖性细胞事件，如神经递质释放。它们在质膜上的丰度是决定BK电流从而调节钙依赖性事件的一个重要因素。在本文中，我们表明，内质网（ER）膜蛋白ERG - 28通过保护SLO - 1 BK通道避免过早降解，促进其从内质网到质膜的转运。在没有ERG - 28的情况下，SLO - 1通道会经历天冬氨酸蛋白酶DDI - 1依赖性降解，导致突触前末端的表达显著降低。ERG - 28缺失抑制了功能获得型突变体在运动、神经递质释放以及AWC嗅觉神经元对的钙介导不对称分化方面的表型缺陷，并赋予了显著的抗乙醇运动行为，类似于功能缺失型突变体，尽管程度较轻。因此，我们的研究表明，BK通道转运的控制是突触传递和神经功能的关键调节机制。
