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Using expression cloning in<jats:italic>Xenopus<\/jats:italic>oocytes coexpressing the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel, the beta-2 adrenergic receptor (\u03b2<jats:sub>2<\/jats:sub>AR), and fractions of a zebrafish cDNA library, we isolated a cDNA clone encoding receptor activity\u2013modifying protein (RAMP)-like triterpene glycoside receptor (RL-TGR), a novel coreceptor involved in signaling in response to triterpene glycosides. This coreceptor appears to be structurally and functionally related to RAMPs, a family of coreceptors that physically associate with and modify the activity of G protein\u2013coupled receptors (GPCRs). In membranes from formoside-responsive oocytes, RL-TGR was immunoprecipitated in an apparent complex with \u03b2<jats:sub>2<\/jats:sub>AR. In HEK293 cells, coexpression of \u03b2<jats:sub>2<\/jats:sub>AR induced the trafficking of RL-TGR from the cytoplasm to the plasma membrane. These results suggest that RL-TGR in the predatory fish physically associates with the \u03b2<jats:sub>2<\/jats:sub>AR or another, more physiologically relevant GPCR and modifies its pharmacology to respond to triterpene glycosides found in sponges that serve as a potential food source for the fish. RL-TGR forms a coreceptor that responds to a chemical defense compound in the marine environment, and its discovery might lead the way to the identification of other receptors that mediate chemical defense signaling.<\/jats:p>","DOI":"10.1073\/pnas.1000343107","type":"journal-article","created":{"date-parts":[[2010,6,22]],"date-time":"2010-06-22T02:44:55Z","timestamp":1277174695000},"page":"12339-12344","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":15,"title":["Identification of RL-TGR, a coreceptor involved in aversive chemical signaling"],"prefix":"10.1073","volume":"107","author":[{"given":"Staci P.","family":"Cohen","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Emory University and Children's Healthcare of Atlanta Center for Cystic Fibrosis Research, Atlanta, GA 30332;"},{"name":"School of Biology, Georgia Institute of Technology, Atlanta, GA 30322;"}]},{"given":"Karla K. V.","family":"Haack","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory University and Children's Healthcare of Atlanta Center for Cystic Fibrosis Research, Atlanta, GA 30332;"},{"name":"School of Biology, Georgia Institute of Technology, Atlanta, GA 30322;"}]},{"given":"Gwyneth E.","family":"Halstead-Nussloch","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory University and Children's Healthcare of Atlanta Center for Cystic Fibrosis Research, Atlanta, GA 30332;"},{"name":"School of Biology, Georgia Institute of Technology, Atlanta, GA 30322;"}]},{"given":"Karen F.","family":"Bernard","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory University and Children's Healthcare of Atlanta Center for Cystic Fibrosis Research, Atlanta, GA 30332;"}]},{"given":"Hanns","family":"Hatt","sequence":"additional","affiliation":[{"name":"Department of Cell Physiology, Ruhr-Universitaet Bochum, 44780 Bochum, Germany; and"}]},{"given":"Julia","family":"Kubanek","sequence":"additional","affiliation":[{"name":"School of Biology, Georgia Institute of Technology, Atlanta, GA 30322;"},{"name":"Department of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332"}]},{"given":"Nael A.","family":"McCarty","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory University and Children's Healthcare of Atlanta Center for Cystic Fibrosis Research, Atlanta, GA 30332;"}]}],"member":"341","published-online":{"date-parts":[[2010,6,3]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1021\/cr00021a012","article-title":"Marine invertebrate chemical defenses","volume":"93","author":"Pawlik JR","year":"1993","unstructured":"JR Pawlik, Marine invertebrate chemical defenses. 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