RRC ID 65248
著者 Cheung TP, Choe JY, Richmond JE, Kim H.
タイトル BK channel density is regulated by endoplasmic reticulum associated degradation and influenced by the SKN-1A/NRF1 transcription factor.
ジャーナル PLoS Genet
Abstract 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.
巻・号 16(6)
ページ e1008829
公開日 2020-6-1
DOI 10.1371/journal.pgen.1008829
PII PGENETICS-D-20-00044
PMID 32502151
PMC PMC7299407
MeSH Aldicarb / pharmacology Animals Animals, Genetically Modified Caenorhabditis elegans / drug effects Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / metabolism* DNA-Binding Proteins / metabolism* Endoplasmic Reticulum / metabolism Endoplasmic Reticulum-Associated Degradation / genetics* Excitation Contraction Coupling / drug effects Excitation Contraction Coupling / genetics Feedback, Physiological / drug effects Large-Conductance Calcium-Activated Potassium Channels / metabolism* Membrane Proteins / metabolism Muscles / innervation Presynaptic Terminals / drug effects Presynaptic Terminals / metabolism* Proteasome Endopeptidase Complex Protein Isoforms / metabolism Transcription Factors / metabolism* Ubiquitin-Protein Ligases / metabolism
IF 5.175
リソース情報
線虫 tm1743 tm4027 tm794 tm2909 tm6098 tm544 tm659