Work

ERG-28 controls BK channel trafficking in the ER to regulate synaptic function and alcohol response in C. elegans

Year: 2017

Type: article

Abstract: 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.

Source: eLife

DOI: 10.7554/elife.24733

Authors: Kelly H Oh, James J Haney, Xiaohong Wang, Chiou-Fen Chuang, Janet E Richmond, Hongkyun Kim

Institutions: Rosalind Franklin University of Medicine and Science, Lake Forest College, Cincinnati Children's Hospital Medical Center, University of Illinois Chicago

Language: English

Topic: Ion channel regulation and function

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $2,500

Funders: Alfred P. Sloan Foundation, National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, National Institute of General Medical Sciences