The Caenorhabditis elegans Iodotyrosine Deiodinase Ortholog SUP-18 Functions through a Conserved Channel SC-Box to Regulate the Muscle Two-Pore Domain Potassium Channel SUP-9
Loss-of-function mutations in the Caenorhabditis elegans gene sup-18 suppress the defects in muscle contraction conferred by a gain-of-function mutation in SUP-10, a presumptive regulatory subunit of the SUP-9 two-pore domain K+ channel associated with muscle membranes. We cloned sup-18 and found th...
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| Format: | Article |
| Language: | en_US |
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Public Library of Science
2014
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| Online Access: | http://hdl.handle.net/1721.1/86089 https://orcid.org/0000-0002-9964-9613 |
| _version_ | 1811097262621720576 |
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| author | de la Cruz, Ignacio Perez Ma, Long Horvitz, Howard Robert |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology de la Cruz, Ignacio Perez Ma, Long Horvitz, Howard Robert |
| author_sort | de la Cruz, Ignacio Perez |
| collection | MIT |
| description | Loss-of-function mutations in the Caenorhabditis elegans gene sup-18 suppress the defects in muscle contraction conferred by a gain-of-function mutation in SUP-10, a presumptive regulatory subunit of the SUP-9 two-pore domain K+ channel associated with muscle membranes. We cloned sup-18 and found that it encodes the C. elegans ortholog of mammalian iodotyrosine deiodinase (IYD), an NADH oxidase/flavin reductase that functions in iodine recycling and is important for the biosynthesis of thyroid hormones that regulate metabolism. The FMN-binding site of mammalian IYD is conserved in SUP-18, which appears to require catalytic activity to function. Genetic analyses suggest that SUP-10 can function with SUP-18 to activate SUP-9 through a pathway that is independent of the presumptive SUP-9 regulatory subunit UNC-93. We identified a novel evolutionarily conserved serine-cysteine-rich region in the C-terminal cytoplasmic domain of SUP-9 required for its specific activation by SUP-10 and SUP-18 but not by UNC-93. Since two-pore domain K+ channels regulate the resting membrane potentials of numerous cell types, we suggest that the SUP-18 IYD regulates the activity of the SUP-9 channel using NADH as a coenzyme and thus couples the metabolic state of muscle cells to muscle membrane excitability. |
| first_indexed | 2024-09-23T16:56:58Z |
| format | Article |
| id | mit-1721.1/86089 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:56:58Z |
| publishDate | 2014 |
| publisher | Public Library of Science |
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| spelling | mit-1721.1/860892022-09-29T22:34:41Z The Caenorhabditis elegans Iodotyrosine Deiodinase Ortholog SUP-18 Functions through a Conserved Channel SC-Box to Regulate the Muscle Two-Pore Domain Potassium Channel SUP-9 de la Cruz, Ignacio Perez Ma, Long Horvitz, Howard Robert Massachusetts Institute of Technology. Department of Biology de la Cruz, Ignacio Perez Horvitz, H. Robert Loss-of-function mutations in the Caenorhabditis elegans gene sup-18 suppress the defects in muscle contraction conferred by a gain-of-function mutation in SUP-10, a presumptive regulatory subunit of the SUP-9 two-pore domain K+ channel associated with muscle membranes. We cloned sup-18 and found that it encodes the C. elegans ortholog of mammalian iodotyrosine deiodinase (IYD), an NADH oxidase/flavin reductase that functions in iodine recycling and is important for the biosynthesis of thyroid hormones that regulate metabolism. The FMN-binding site of mammalian IYD is conserved in SUP-18, which appears to require catalytic activity to function. Genetic analyses suggest that SUP-10 can function with SUP-18 to activate SUP-9 through a pathway that is independent of the presumptive SUP-9 regulatory subunit UNC-93. We identified a novel evolutionarily conserved serine-cysteine-rich region in the C-terminal cytoplasmic domain of SUP-9 required for its specific activation by SUP-10 and SUP-18 but not by UNC-93. Since two-pore domain K+ channels regulate the resting membrane potentials of numerous cell types, we suggest that the SUP-18 IYD regulates the activity of the SUP-9 channel using NADH as a coenzyme and thus couples the metabolic state of muscle cells to muscle membrane excitability. National Institutes of Health (U.S.) (NIH Grant GM24663) National Science Foundation (U.S.) (Graduate Research Fellowship by NSFC Grant 31371253) National Institutes of Health (U.S.) (NIH predoctoral training grant) Howard Hughes Medical Institute (Investigator) 2014-04-09T20:24:46Z 2014-04-09T20:24:46Z 2014-02 2013-10 Article http://purl.org/eprint/type/JournalArticle 1553-7404 http://hdl.handle.net/1721.1/86089 De la Cruz, Ignacio Perez, Long Ma, and H. Robert Horvitz. “The Caenorhabditis Elegans Iodotyrosine Deiodinase Ortholog SUP-18 Functions through a Conserved Channel SC-Box to Regulate the Muscle Two-Pore Domain Potassium Channel SUP-9.” Edited by L. Rene Garcia. PLoS Genet 10, no. 2 (February 20, 2014): e1004175. https://orcid.org/0000-0002-9964-9613 en_US http://dx.doi.org/10.1371/journal.pgen.1004175 PLoS Genetics Creative Commons Attribution http://creativecommons.org/licenses/by/4.0/ application/pdf Public Library of Science PLoS |
| spellingShingle | de la Cruz, Ignacio Perez Ma, Long Horvitz, Howard Robert The Caenorhabditis elegans Iodotyrosine Deiodinase Ortholog SUP-18 Functions through a Conserved Channel SC-Box to Regulate the Muscle Two-Pore Domain Potassium Channel SUP-9 |
| title | The Caenorhabditis elegans Iodotyrosine Deiodinase Ortholog SUP-18 Functions through a Conserved Channel SC-Box to Regulate the Muscle Two-Pore Domain Potassium Channel SUP-9 |
| title_full | The Caenorhabditis elegans Iodotyrosine Deiodinase Ortholog SUP-18 Functions through a Conserved Channel SC-Box to Regulate the Muscle Two-Pore Domain Potassium Channel SUP-9 |
| title_fullStr | The Caenorhabditis elegans Iodotyrosine Deiodinase Ortholog SUP-18 Functions through a Conserved Channel SC-Box to Regulate the Muscle Two-Pore Domain Potassium Channel SUP-9 |
| title_full_unstemmed | The Caenorhabditis elegans Iodotyrosine Deiodinase Ortholog SUP-18 Functions through a Conserved Channel SC-Box to Regulate the Muscle Two-Pore Domain Potassium Channel SUP-9 |
| title_short | The Caenorhabditis elegans Iodotyrosine Deiodinase Ortholog SUP-18 Functions through a Conserved Channel SC-Box to Regulate the Muscle Two-Pore Domain Potassium Channel SUP-9 |
| title_sort | caenorhabditis elegans iodotyrosine deiodinase ortholog sup 18 functions through a conserved channel sc box to regulate the muscle two pore domain potassium channel sup 9 |
| url | http://hdl.handle.net/1721.1/86089 https://orcid.org/0000-0002-9964-9613 |
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