The calcium-activated potassium channel, SLO-1, reduces cellular excitability in response to high levels of calcium increases. This physiological property is essential for maintaining calcium homeostasis and proper excitability. To understand how the SLO-1 channel is regulated, we performed a genetic suppressor screen that takes advantage of sluggish, uncoordinated locomotory phenotype of gain-of-function
slo-1(
ky399) mutants. From this screen, we previously identified the alpha-catulin homologue,
ctn-1, that encodes a cytoskeletal protein involved in localization of the SLO-1 channel at the presynaptic terminals and near dense bodies of muscle. In the same genetic screen, we also identified a
cim16 mutation that suppresses the locomotory phenotype of
slo-1(
ky399). However,
cim16 mutants do not show the head-bending phenotype, a hallmark phenotype of loss-of-function mutants in genes encoding
slo-1 and components of the dystrophin complex. To further understand the regulatory role of
cim16 for SLO-1, we cloned
cim16 by a combination of genetic mapping and transgenic rescue.
cim16 has a mutation in the
erg-28 gene, a conserved gene in eukaryotes. ERG-28 is originally identified in yeast as a protein that anchors ergosterol (sterol found in fungi) biosynthetic enzymes. However, our data indicate that ERG-28 is not involved in sterol synthesis. First, we found that other mutants defective in genes involved in sterol biosynthesis cannot suppress the locomotory defects of
slo-1(
ky399). Second, our tissue specific rescue experiments show that neuronal, but not muscle, expression of
erg-28 reverts normal locomotion of
cim16;
slo-1(
ky399) to the sluggish, uncoordinated locomotory phenotype of
slo-1(
ky399), strongly suggesting that
erg-28 has a neuronal tissue specific role, as opposed to a role in the synthesis of diffusible sterol. One possibility is that ERG-28 is involved in neuronal trafficking of the SLO-1 channels. However, the localization of SLO-1 at presynaptic terminals is not obviously altered by
cim16 mutation. To verify this finding we are analyzing additional
erg-28 alleles. At the same time, we are exploring the possibility that
erg-28 mutations alter an accessory subunit of SLO-1.