α‐Catulin CTN‐1 is required for BK channel subcellular localization in C. elegans body‐wall muscle cells

The BK channel, a voltage‐ and Ca 2+ ‐gated large‐conductance potassium channel with many important functions, is often localized at specific subcellular domains. Although proper subcellular localization is likely a prerequisite for the channel to perform its physiological functions, little is known about the molecular basis of localization. Here, we show that CTN‐1, a homologue of mammalian α‐catulin, is required for subcellular localization of SLO‐1, the Caenorhabditis elegans BK channel α‐subunit, in body‐wall muscle cells. CTN‐1 was identified in a genetic screen for mutants that suppressed a lethargic phenotype caused by expressing a gain‐of‐function ( gf ) isoform of SLO‐1. In body‐wall muscle cells, CTN‐1 coclusters with SLO‐1 at regions of dense bodies, which are Z‐disk analogs of mammalian skeletal muscle. In ctn‐1 loss‐of‐function (lf) mutants, SLO‐1 was mislocalized in body‐wall muscle but its transcription and protein level were unchanged. Targeted rescue of ctn‐1(lf) in muscle was sufficient to reinstate the lethargic phenotype in slo‐1(gf);ctn‐1(lf) . These results suggest that CTN‐1 plays an important role in BK channel function by mediating channel subcellular localization.