Kim Lab
Projects in the lab
1. We use Caenorhabditis elegans as a model organsim to understand how ion channels are mobilized to subcellular domains and form a channel cluster at their target sites. Our favorite channel is the CaV2 voltage-gated calcium channel. The CaV2 channel mediates presynaptic calcium influx, which triggers the fusion of neurotransmitter-filled synaptic vesicles to the presynaptic plasma membrane. We discovered that, as in mammals, the UNC-2 channel, the sole C. elegans ortholog of CaV2 channels, is tethered to the presynaptic terminal by redundant interactions between active zone scaffold proteins. However, RIM/UNC-10 and Liprin-alpha/SYD-2 proteins play a prominent roles in UNC-2 localization.
2. The other channel we focus on is the calcium-activated potassium BK channel (SLO-1), which mediates acute alcohol intoxication and tolerance in C. elegans and mammals. Loss-of-function slo-1 mutants exhibit a strong resistance to an intoxicating dose of alcohol.
What happens to BK SLO-1 channels when not tethered at presynpatic terminals?
Sup_video2.mp4Time lapse imaging of BK SLO-1 channels in axon terminals of wild-type and ctn-1 mutant animals. ctn-1 mutant animals have a normal level of SLO-1 channels, but have a defect in channel clustering.
Sup_Video1.mp4BK SLO-1 channel clustering is essential for acute acohol intoxication (Oh and Kim, Sci Rep, 2019). ctn-1 mutant animals show an ethanol-resistant locomotor behavior comparable to that of slo-1 loss-of-function mutant animals
3. Chronic alcohol consumption causes tissue injury and organ damage, including brains, skeletal muscle, and liver. We use C. elegans to tackle on alcohol-related neurological disorders, such as alcoholic myopathy, alcoholic neuropathy, alcoholic neurodegeneration. We have found that the primary target of alcohol is centered on mitochondria, a cellular powerplant. Eiliciting the protective response for mitochondria allows C. elegans to maintain normal movement even after long-term alcohol exposure.
Video S1.mp4C. elegans swims in a liquid medium. Animals exposed to a low concentration of ethanol for 24 h fail to show this robust swimming behavior. atfs-1(gf) mutants that have an elevated mitochondrial stress response show robust swimming even after 24 h ethanol exposure. (Oh, et al. 2020, FASEB J.)