RRC ID 5712
著者 Kim H, Pierce-Shimomura JT, Oh HJ, Johnson BE, Goodman MB, McIntire SL.
タイトル The dystrophin complex controls bk channel localization and muscle activity in Caenorhabditis elegans.
ジャーナル PLoS Genet
Abstract Genetic defects in the dystrophin-associated protein complex (DAPC) are responsible for a variety of pathological conditions including muscular dystrophy, cardiomyopathy, and vasospasm. Conserved DAPC components from humans to Caenorhabditis elegans suggest a similar molecular function. C. elegans DAPC mutants exhibit a unique locomotory deficit resulting from prolonged muscle excitation and contraction. Here we show that the C. elegans DAPC is essential for proper localization of SLO-1, the large conductance, voltage-, and calcium-dependent potassium (BK) channel, which conducts a major outward rectifying current in muscle under the normal physiological condition. Through analysis of mutants with the same phenotype as the DAPC mutants, we identified the novel islo-1 gene that encodes a protein with two predicted transmembrane domains. We demonstrate that ISLO-1 acts as a novel adapter molecule that links the DAPC to SLO-1 in muscle. We show that a defect in either the DAPC or ISLO-1 disrupts normal SLO-1 localization in muscle. Consistent with observations that SLO-1 requires a high calcium concentration for full activation, we find that SLO-1 is localized near L-type calcium channels in muscle, thereby providing a mechanism coupling calcium influx with the outward rectifying current. Our results indicate that the DAPC modulates muscle excitability by localizing the SLO-1 channel to calcium-rich regions of C. elegans muscle.
巻・号 5(12)
ページ e1000780
公開日 2009-12-1
DOI 10.1371/journal.pgen.1000780
PMID 20019812
PMC PMC2788698
MeSH Animals Caenorhabditis elegans Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Calcium Dystrophin Dystrophin-Associated Protein Complex / physiology* Electrophysiology Large-Conductance Calcium-Activated Potassium Channels / genetics Large-Conductance Calcium-Activated Potassium Channels / metabolism* Muscles / physiology* Mutant Proteins
IF 5.175
引用数 39
WOS 分野 GENETICS & HEREDITY
リソース情報
線虫 tm2709 tm2737