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.
Chen
Bojun
B
Department of Neuroscience, University of Connecticut Health Center, Farmington, CT, USA.
Liu
Ping
P
Wang
Sijie J
SJ
Ge
Qian
Q
Zhan
Haiying
H
Mohler
William A
WA
Wang
Zhao-Wen
ZW
D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D032342:Muscle Cells / Q000378:metabolism*; D009865:Oocytes / Q000378:metabolism; D010641:Phenotype; D017386:Sequence Homology, Amino Acid; D013347:Subcellular Fractions; D014982:Xenopus laevis; D051178:alpha Catenin / Q000235:genetics / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D051036:Large-Conductance Calcium-Activated Potassium Channels; D051178:alpha Catenin; C494845:slo-1 protein, C elegans