Essential molecular determinants for thyroid hormone transport and first structural implications for monocarboxylate transporter 8.

The Journal of Biological Chemistry
Anita KinneUlrich Schweizer

Abstract

Monocarboxylate transporter 8 (MCT8, SLC16A2) is a thyroid hormone (TH) transmembrane transport protein mutated in Allan-Herndon-Dudley syndrome, a severe X-linked psychomotor retardation. The neurological and endocrine phenotypes of patients deficient in MCT8 function underscore the physiological significance of carrier-mediated TH transmembrane transport. MCT8 belongs to the major facilitator superfamily of 12 transmembrane-spanning proteins and mediates energy-independent bidirectional transport of iodothyronines across the plasma membrane. Structural information is lacking for all TH transmembrane transporters. To gain insight into structure-function relations in TH transport, we chose human MCT8 as a paradigm. We systematically performed conventional and liquid chromatography-tandem mass spectrometry-based uptake measurements into MCT8-transfected cells using a large number of compounds structurally related to iodothyronines. We found that human MCT8 is specific for L-iodothyronines and requires at least one iodine atom per aromatic ring. Neither thyronamines, decarboxylated metabolites of iodothyronines, nor triiodothyroacetic acid and tetraiodothyroacetic acid, TH derivatives lacking both chiral center and amino group, a...Continue Reading

References

Dec 14, 1995·Nature·R L WagnerR J Fletterick
Jun 20, 1993·Journal of Molecular Biology·R A LaskowskiJ M Thornton
Feb 27, 2001·Molecular Endocrinology·R L WagnerR J Fletterick
May 10, 2003·Pflügers Archiv : European journal of physiology·Andrew P Halestrap, David Meredith
Jul 23, 2003·The Journal of Biological Chemistry·Edith C H FriesemaTheo J Visser
May 18, 2004·Nature Medicine·Thomas S ScanlanDavid K Grandy
Nov 24, 2004·Biophysical Journal·Peter Werner HildebrandCornelius Frömmel
Sep 1, 2005·Thyroid : Official Journal of the American Thyroid Association·Sing-Yung WuInder J Chopra
Jun 20, 2006·Journal of Molecular Biology·Alessandro S NascimentoIgor Polikarpov
Feb 24, 2007·The Journal of Clinical Investigation·Marija TrajkovicHeike Heuer
Sep 12, 2007·Bioinformatics·M A LarkinD G Higgins
Mar 14, 2008·Molecular Endocrinology·Edith C H FriesemaTheo J Visser
Mar 15, 2008·Endocrinology·S PiehlJ Köhrle
Apr 10, 2008·European Journal of Human Genetics : EJHG·Suzanna Gerarda Maria FrintsAndreas Walter Kuss
Jul 19, 2008·Human Mutation·W Edward VisserTheo J Visser
Dec 17, 2008·Endocrinology·Alexandra G IanculescuThomas S Scanlan
Feb 6, 2009·Annals of Neurology·Catherine Vaurs-BarrièreRenaud Touraine
Jul 31, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Eva K WirthUlrich Schweizer
Aug 4, 2009·Journal of Molecular Endocrinology·Anita KinneUlrich Schweizer
Oct 3, 2009·Endocrinology·W Edward VisserTheo J Visser
Jan 20, 2010·Molecular and Cellular Endocrinology·Edith C H FriesemaTheo J Visser

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Citations

Nov 20, 2012·The Journal of Biological Chemistry·Gad David VatineLior Appelbaum
Aug 13, 2011·Thyroid Research·Anita KinneGerd Krause
May 6, 2014·Toxicology and Applied Pharmacology·Branka Šošić-JurjevićJosef Köhrle
Aug 15, 2012·Biochimica Et Biophysica Acta·Ulrich Schweizer, Josef Köhrle
Mar 5, 2013·Toxicology in Vitro : an International Journal Published in Association with BIBRA·AlberTinka J MurkArno C Gutleb
Jun 8, 2014·Current Opinion in Structural Biology·Torsten H Walther, Anne S Ulrich
Jul 13, 2011·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Maria Carolina de Souza Dos SantosDenise Pires de Carvalho
Jul 11, 2014·Frontiers in Endocrinology·Eva K WirthJosef Köhrle
Dec 21, 2014·Journal of Molecular Endocrinology·Jana FischerHeike Biebermann
Jan 11, 2016·Acta Physiologica·D GnocchiP Parini
Aug 6, 2016·Molecular and Cellular Endocrinology·Alies A van MullemTheo J Visser
Sep 22, 2016·Thyroid : Official Journal of the American Thyroid Association·Carolin Stephanie HoefigJosef Köhrle
Jan 31, 2017·Molecular and Cellular Endocrinology·Ulrich SchweizerClemens Steegborn
Jan 26, 2017·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Hongyan Dong, Michael G Wade
Apr 25, 2015·Endocrinology·Roopa Jayarama-NaiduKostja Renko
Oct 12, 2010·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Emi KimotoDavid B Duignan
Nov 23, 2019·Endocrine Reviews·Stefan GroenewegW Edward Visser
Sep 11, 2019·Biological Trace Element Research·Shiqiao PengWeiping Teng
Aug 10, 2011·Current Opinion in Endocrinology, Diabetes, and Obesity·Juan Bernal
Jun 1, 2016·Molecular Endocrinology·Jörg JohannesUlrich Schweizer
Apr 3, 2013·Endocrinology·Elaine C Lima de SouzaTheo J Visser
Apr 14, 2016·Endocrinology·Nele M A BourgeoisTheo J Visser
Jun 26, 2013·Endocrinology·Alexandro J MartagónPaul Webb
May 27, 2016·Angewandte Chemie·Santanu MondalGovindasamy Mugesh
Aug 23, 2019·Thyroid : Official Journal of the American Thyroid Association·Stefan GroenewegTheo J Visser
Jul 30, 2020·Journal of the Endocrine Society·Stefan GroenewegW Edward Visser

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