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 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. © 2014 de la cruz et al.