We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
The Dystrophin Complex Controls BK Channel Localization and Muscle Activity in Caenorhabditis elegans.
- Authors
Hongkyun Kim; Pierce-Shimomura, Jonathan T.; Oh, Hyun J.; Johnson, Brandon E.; Goodman, Miriam B.; McIntire, Steven L.
- 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.
- Publication
PLoS Genetics, 2009, Vol 5, Issue 12, p1
- ISSN
1553-7390
- Publication type
Academic Journal
- DOI
10.1371/journal.pgen.1000780