The SLO-1 BK Channel is a calcium-activated potassium channel that controls synaptic transmission and muscle excitation. The overall density of SLO-1 channels is primarily regulated at the level of channel trafficking. However, the mechanism underlying BK channel trafficking has yet to be clearly defined. In a previous C. elegans genetic study, the ER membrane protein ERG-28 was identified as a regulator of SLO-1 trafficking from the ER to the Golgi complex; SLO-1 level is drastically reduced in the absence of ERG-28. We hypothesize that without ERG-28, SLO-1 is recognized by the ERAD (ER associated degradation) system and inactivation of ERAD increases SLO-1 channel level. Using a candidate gene approach, we identified
sel-11, encoding an ER-resident E3 ubiquitin ligase, as an important regulator of SLO-1 degradation in
erg-28 mutants. Introduction of
sel-11 mutation to
erg-28 mutants resulted in significant recovery of SLO-1 levels at the plasma membrane. Moreover, the recovered SLO-1 at the plasma membrane is functional as
sel-11 mutation suppressed
erg-28 mutant phenotype. To further ascertain this finding, we determined whether members of the canonical
sel-11-mediated degradation pathway influence SLO-1 channel levels. We indeed found that
sel-1 and
cdc-48.2 mediates SLO-1 degradation in
erg-28 mutants. We previously uncovered that
ddi-1, a gene encoding an aspartic protease, participates in the degradation of SLO-1. Based on our new findings, we examined the relationship between
ddi-1 and
sel-11. The SLO-1 channel levels of
ddi-1;
sel-11 erg-28 triple mutant and
sel-11 erg-28 or
ddi-1;
erg-28 double mutants were not significantly different, suggesting a shared pathway of SLO-1 degradation between SEL-11 and DDI-1. Together, our data show that the overall level of SLO-1 channels is regulated in the ER by the concerted action between ERG-28 and the ERAD machinery, in which SEL-11 and DDI-1 are major components.