Slo2 potassium channel function depends on a SCYL1 protein

Slo2 potassium channels play important roles in neuronal function, and their mutations in humans cause epilepsies and profound cognitive defects. However, little is known how Slo2 function is regulated by other proteins. In a genetic screen for suppressors of a sluggish phenotype caused by a hyperactive C. elegans Slo2 (SLO-2), mutants of adr-1, a gene important to RNA editing, were isolated. SLO-2 current in motor neurons is substantially decreased in the mutants. However, slo-2 transcripts have no detectable RNA editing events and exhibit a similar expression level in wild type and adr-1 mutants. In contrast, mRNA level of scyl-1, which encodes an orthologue of mammalian SCYL1 (a pseudokinase), is greatly reduced in adr-1 mutants due to deficient RNA editing at a single adenosine in its 3’-UTR. SCYL-1 physically interacts with SLO-2 in neurons. Single-channel open probability of SLO-2 in neurons is reduced by ~50% in scyl-1 knockout whereas that of human Slo2.2/Slack is doubled by SCYL1 in a heterologous expression system. These results suggest that SCYL-1/SCYL1 is an evolutionarily conserved regulator of Slo2 channels. Examination of gene expression in wild type and adr-1 mutant worms in three biological replicates.