An alpha-catulin homologue controls neuromuscular function through localization of the dystrophin complex and BK channels in Caenorhabditis elegans

The large conductance,voltage- and calcium-dependent potassium (bk) channel serves as a major negative feedback regulator of calcium-mediated physiological processes and has been implicated in muscle dysfunction and neurological disorders. in addition to membrane depolarization,activation of the bk channel requires a rise in cytosolic calcium. localization of the bk channel near calcium channels is therefore critical for its function. in a genetic screen designed to isolate novel regulators of the caenorhabditis elegans bk channel,slo-1,we identified ctn-1,which encodes an a-catulin homologue with homology to the cytoskeletal proteins a-catenin and vinculin. ctn-1 mutants resemble slo-1 loss-offunction mutants,as well as mutants with a compromised dystrophin complex. we determined that ctn-1 uses two distinct mechanisms to localize slo-1 in muscles and neurons. in muscles,ctn-1 utilizes the dystrophin complex to localize slo-1 channels near l-type calcium channels. in neurons,ctn-1 is involved in localizing slo-1 to a specific domain independent of the dystrophin complex. our results demonstrate that ctn-1 ensures the localization of slo-1 within calcium nanodomains,thereby playing a crucial role in muscles and neurons. © 2010 abraham et al.