Ion channels are present at specific levels within subcellular compartments of excitable cells. The regulation of ion channel trafficking and targeting is an effective way to control cell excitability. The BK channel is a calcium-activated potassium channel that serves as a negative feedback mechanism at presynaptic axon terminals and sites of muscle excitation. The C. elegans BK channel ortholog, SLO-1, requires an endoplasmic reticulum (ER) membrane protein for efficient anterograde transport to these locations. Here, we found that, in the absence of this ER membrane protein, SLO-1 channels that are seemingly normally folded and expressed at physiological levels undergo SEL-11/HRD1-mediated ER-associated degradation (ERAD). This SLO-1 degradation is also indirectly regulated by a SKN-1A/NRF1-mediated transcriptional mechanism that controls proteasome levels. Therefore, our data indicate that SLO-1 channel density is regulated by the competitive balance between the efficiency of ER trafficking machinery and the capacity of ERAD.

离子通道以特定水平存在于可激发细胞的亚细胞区室中。离子通道运输和靶向的调节是控制细胞兴奋性的有效方法。BK通道是钙激活的钾通道，在突触前轴突末端和肌肉兴奋部位充当负反馈机制。该Ç。线虫BK通道直向同源物SLO-1需要内质网（ER）膜蛋白才能有效地顺行转运到这些位置。在这里，我们发现，在没有这种ER膜蛋白的情况下，似乎正常折叠并以生理水平表达的SLO-1通道会经历SEL-11 / HRD1介导的ER相关降解（ERAD）。这种SLO-1降解也受控制蛋白酶体水平的SKN-1A / NRF1介导的转录机制间接调控。因此，我们的数据表明SLO-1通道密度受ER贩运机效率与ERAD能力之间竞争性平衡的调节。