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PLoS Genet. 2009 Dec;5(12):e1000780. doi: 10.1371/journal.pgen.1000780. Epub 2009 Dec 18.

The dystrophin complex controls bk channel localization and muscle activity in Caenorhabditis elegans.

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  • 1Department of Cell Biology and Anatomy, The Chicago Medical School, Rosalind Franklin University of Science and Medicine, North Chicago, Illinois, United States of America. hongkyun.kim@rosalindfranklin.edu

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.

PMID:
20019812
[PubMed - indexed for MEDLINE]
PMCID:
PMC2788698
Free PMC Article
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