title: Trace Amine-Associated Receptor 1 Localization at the Apical Plasma Membrane Domain of Fisher Rat Thyroid Epithelial Cells Is Confined to Cilia.
abstract: BACKGROUND
  The trace amine-associated receptor 1 (Taar1) is one member of the Taar family of G-protein-coupled receptors (GPCR) accepting various biogenic amines as ligands. It has been proposed that Taar1 mediates rapid, membrane-initiated effects of thyronamines, the endogenous decarboxylated and deiodinated relatives of the classical thyroid hormones T4 and T3.
  
  
  OBJECTIVE
  Although the physiological actions of thyronamines in general and 3-iodothyronamine (T1AM) in particular are incompletely understood, studies published to date suggest that synthetic T1AM-activated Taar1 signaling antagonizes thyromimetic effects exerted by T3. However, the location of Taar1 is currently unknown.
  
  
  METHODS
  To fill this gap in our knowledge we employed immunofluorescence microscopy and a polyclonal antibody to detect Taar1 protein expression in thyroid tissue from Fisher rats, wild-type and taar1-deficient mice, and in the polarized FRT cells.
  
  
  RESULTS
  With this approach we found that Taar1 is expressed in the membranes of subcellular compartments of the secretory pathway and on the apical plasma membrane of FRT cells. Three-dimensional analyses further revealed Taar1 immunoreactivity in cilial extensions of postconfluent FRT cell cultures that had formed follicle-like structures.
  
  
  CONCLUSIONS
  The results suggest Taar1 transport along the secretory pathway and its accumulation in the primary cilium of thyrocytes. These findings are of significance considering the increasing interest in the role of cilia in harboring functional GPCR. We hypothesize that thyronamines can reach and activate Taar1 in thyroid follicular epithelia by acting from within the thyroid follicle lumen, their potential site of synthesis, as part of a nonclassical mechanism of thyroid autoregulation.
authors.affiliation: Department of Life Sciences and Chemistry, Jacobs University Bremen, Bremen, Germany.
authors.forename: Joanna
authors.initials: J
authors.lastname: Szumska
authors.affiliation: Department of Life Sciences and Chemistry, Jacobs University Bremen, Bremen, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Qatato
authors.affiliation: Department of Life Sciences and Chemistry, Jacobs University Bremen, Bremen, Germany.
authors.forename: Maren
authors.initials: M
authors.lastname: Rehders
authors.affiliation: Department of Endocrinology and Metabolism and Division of Laboratory Research, University of Duisburg-Essen, Essen, Germany.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Führer
authors.affiliation: Institut für Experimentelle Pädiatrische Endokrinologie, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Biebermann
authors.affiliation: Department of Physiology and Pharmacology, School of Medicine and the Knight Cardiovascular Institute, Oregon Health & Science University, Portland, Oreg., USA.
authors.forename: David K
authors.initials: DK
authors.lastname: Grandy
authors.affiliation: Institut für Experimentelle Endokrinologie, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Josef
authors.initials: J
authors.lastname: Köhrle
authors.affiliation: Department of Life Sciences and Chemistry, Jacobs University Bremen, Bremen, Germany.
authors.forename: Klaudia
authors.initials: K
authors.lastname: Brix
keywords: G-protein-coupled receptors; Taar1; Thyroid follicle; Thyroid gland; Thyroid hormones; Thyronamines