ERG-28 controls BK channel trafficking in the ER to regulate synaptic function and alcohol response in C. elegans
ERG-28 controls BK channel trafficking in the ER to regulate synaptic function and alcohol response in C. elegans
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DOI：
10.7554/elife.24733
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发表时间：
2017-02-07
期刊：
影响因子：
7.7
通讯作者：
Kim, Hongkyun
中科院分区：
文献类型：
--
作者：
Oh, Kelly H.;Haney, James J.;Kim, Hongkyun
电压和钙依赖性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。它们的质膜丰度是决定BK电流并因此调节钙依赖性事件的重要因素。In C. elegans，我们表明，ERG-28，内质网（ER）膜蛋白，促进运输的SLO-1 BK通道从ER到质膜的保护他们从过早降解。在缺乏ERG-28的情况下，SLO-1通道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的丢失抑制了AWC嗅觉神经元对的运动、神经递质释放和钙介导的不对称分化中的<$1功能获得性突变体的表型缺陷，并赋予了显著的乙醇抗性运动行为，类似于<$1功能丧失性突变体，尽管程度较小。因此，我们的研究表明，BK通道运输的控制是突触传递和神经功能的关键调节机制。
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 C. elegans, 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 erg-28 suppressed phenotypic defects of slo-1 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 slo-1 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.