ERG-28 controls BK channel trafficking in the ER to regulate synaptic function and alcohol response in C. elegans
Kelly H Oh,
James J Haney,
Xiaohong Wang,
Chiou-Fen Chuang,
Janet E Richmond,
Hongkyun Kim
Affiliations
Kelly H Oh
Department of Cell Biology and Anatomy, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, United States
James J Haney
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
Xiaohong Wang
Division of Developmental Biology, Cincinnati Children’s Hospital Research Foundation, Cincinnati, United States
Chiou-Fen Chuang
Division of Developmental Biology, Cincinnati Children’s Hospital Research Foundation, Cincinnati, United States; Department of Biological Sciences, University of Illinois at Chicago, Chicago, United States
Janet E Richmond
Department of Biological Sciences, University of Illinois at Chicago, Chicago, United States
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.
