ERG-28 controls BK channel trafficking in the ER to regulate synaptic function and alcohol response inC. elegans.
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. InC. 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 oferg-28suppressed phenotypic defects ofslo-1gain-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, resemblingslo-1loss-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.
Department of Cell Biology and Anatomy, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, United States.
Kelly H
KH
Oh
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.
James J
JJ
Haney
Division of Developmental Biology, Cincinnati Children's Hospital Research Foundation, Cincinnati, United States.
Xiaohong
X
Wang
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.
Chiou-Fen
CF
Chuang
Department of Biological Sciences, University of Illinois at Chicago, Chicago, United States.
Janet E
JE
Richmond
Department of Cell Biology and Anatomy, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, United States.
Hongkyun
0000-0002-4879-7122
H
Kim
D000438:Alcohols / Q000378:metabolism*; D000818:Animals; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D021381:Protein Transport; D013569:Synapses / Q000502:physiology*
D000438:Alcohols; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; C000624971:ERG-28 protein, C elegans; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008565:Membrane Proteins; C494845:slo-1 protein, C elegans
BK channel; alcohol; neuroscience; synaptic transmission