BK channel density is regulated by endoplasmic reticulum associated degradation and influenced by the SKN-1A/NRF1 transcription factor

Autoři: Timothy P. Cheung aff001;  Jun-Yong Choe aff002;  Janet E. Richmond aff004;  Hongkyun Kim aff001
Působiště autorů: Center for Cancer Cell Biology, Immunology, and Infection, Department of Cell Biology and Anatomy, Chicago Medical School, Rosalind Franklin University of Medicine & Science, North Chicago, Illinois, United States of America aff001;  School of Graduate & Postdoctoral Studies, Rosalind Franklin University of Medicine & Science, North Chicago, Illinois, United States of America aff002;  Department of Biochemistry and Molecular Biology, Rosalind Franklin University of Medicine & Science, North Chicago, Illinois United States of America aff003;  Department of Biological Sciences, University of Illinois at Chicago, Chicago, Illinois, United States of America aff004
Vyšlo v časopise: BK channel density is regulated by endoplasmic reticulum associated degradation and influenced by the SKN-1A/NRF1 transcription factor. PLoS Genet 16(6): e32767. doi:10.1371/journal.pgen.1008829
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1008829


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.

Klíčová slova:

Caenorhabditis elegans – Deletion mutation – Endoplasmic reticulum – Point mutation – Proteasomes – Scanning electron microscopy – Ubiquitin ligases – Calcium-activated potassium channels


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