title: The A/B domain of the teleost glucocorticoid receptors influences partial nuclear localization in the absence of hormone.
abstract: The glucocorticoid (GR) and mineralocorticoid receptor (MR) of extant jawed vertebrates emerged after duplication of an ancestral corticosteroid receptor. The ancestral corticosteroid receptor resembled extant MRs in hormone selectivity, and the different ligand specificity of extant GRs is a secondary derived characteristic. An additional characteristic that distinguishes the mammalian GR from the MR is the cellular distribution pattern in the absence of hormone: the naïve GR resides in the cytoplasm, whereas the naïve MR is found in both the nucleus and cytoplasm. Our results show, by the use of green fluorescent protein-tagged fusion proteins, that the GRs [rainbow trout (rt) GR1 and rtGR2] from a lower vertebrate, the teleost fish, rainbow trout (Oncorhynchus mykiss) resemble mammalian MR rather than GR in their subcellular localization pattern. The addition of cortisol caused the remaining cytoplasmic rtGR1 and rtGR2 to migrate to the nucleus. The speed of nuclear localization was cortisol concentration dependent, with rtGR2 being more sensitive than rtGR1, mimicking the transactivational properties of the receptors in which the cortisol EC50 value is an order of magnitude lower for rtGR2. By the use of chimera constructs between the trout GRs and the rat GR C656G, we show that the E domain of the trout receptors are not involved in the nucleocytoplasmic localization of naïve trout GRs, but the A/B domain, especially if linked to the corresponding trout CD region, plays a pivotal role in the cellular distribution pattern. This is unrelated to the difference in the trout GRs transactivation sensitivity, which is determined by the receptor's E-domains.
authors.affiliation: Nutritional Sciences Research Division, King's College London, London SE1 9NH, United Kingdom.
authors.forename: Heidi
authors.initials: H
authors.lastname: Becker
authors.forename: Armin
authors.initials: A
authors.lastname: Sturm
authors.forename: James E
authors.initials: JE
authors.lastname: Bron
authors.forename: Kristin
authors.initials: K
authors.lastname: Schirmer
authors.forename: Nicolas R
authors.initials: NR
authors.lastname: Bury
mesh_terms: D000818:Animals; D016466:CHO Cells; D019556:COS Cells; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003412:Cricetulus; D005938:Glucocorticoids / Q000494:pharmacology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D017686:Oncorhynchus mykiss / Q000235:genetics* / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000235:genetics / Q000502:physiology; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins