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An Alpha-Catulin Homologue Controls Neuromuscular Function through Localization of the Dystrophin Complex and BK Channels in Caenorhabditis elegans

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Title: An Alpha-Catulin Homologue Controls Neuromuscular Function through Localization of the Dystrophin Complex and BK Channels in Caenorhabditis elegans
Author(s): Abraham, Linu S.; Oh, Hyun J.; Sancar, Feyza; Richmond, Janet E.; Kim, Hongkyun
Subject(s): BK channel caenorhabditis elegans
Abstract: 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.
Issue Date: 2010-08
Publisher: Public Library of Science
Citation Info: Abraham, L. S., Oh, H. J., Sancar, F., Richmond, J. E., & Kim, H. 2010. An Alpha-Catulin Homologue Controls Neuromuscular Function through Localization of the Dystrophin Complex and BK Channels in Caenorhabditis elegans. Plos Genetics, 6(8). DOI: 10.1371/journal.pgen.1001077
Type: Article
Description: The original version is available through Public Library of Science at DOI: 10.1371/journal.pgen.1001077
URI: http://hdl.handle.net/10027/7607
ISSN: 1553-7390
Sponsor: This work was supported by National Institute of Health grants R01 MH073156 (to JER), start-up funds (to HK), and R01 NS058814 (to HK).
Date Available in INDIGO: 2011-05-11
 

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