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Illuminating the function of the orphan transporter, SLC22A10, in humans and other primates.
Yee, Sook Wah; Ferrández-Peral, Luis; Alentorn-Moron, Pol; Fontsere, Claudia; Ceylan, Merve; Koleske, Megan L; Handin, Niklas; Artegoitia, Virginia M; Lara, Giovanni; Chien, Huan-Chieh; Zhou, Xujia; Dainat, Jacques; Zalevsky, Arthur; Sali, Andrej; Brand, Colin M; Wolfreys, Finn D; Yang, Jia; Gestwicki, Jason E; Capra, John A; Artursson, Per; Newman, John W; Marquès-Bonet, Tomàs; Giacomini, Kathleen M.
Afiliación
  • Yee SW; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, USA.
  • Ferrández-Peral L; Institute of Evolutionary Biology (UPF-CSIC), PRBB, Dr. Aiguader 88, 08003, Barcelona, Spain.
  • Alentorn-Moron P; Institute of Evolutionary Biology (UPF-CSIC), PRBB, Dr. Aiguader 88, 08003, Barcelona, Spain.
  • Fontsere C; Institute of Evolutionary Biology (UPF-CSIC), PRBB, Dr. Aiguader 88, 08003, Barcelona, Spain.
  • Ceylan M; Center for Evolutionary Hologenomics, The Globe Institute, University of Copenhagen, Øster Farimagsgade 5A, 1352, Copenhagen, Denmark.
  • Koleske ML; Department of Pharmacy, Uppsala University, Uppsala, Sweden.
  • Handin N; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, USA.
  • Artegoitia VM; Department of Pharmacy, Uppsala University, Uppsala, Sweden.
  • Lara G; United States Department of Agriculture, Agricultural Research Service, Western Human Nutrition Research Center, Davis, CA, 95616, USA.
  • Chien HC; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, USA.
  • Zhou X; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, USA.
  • Dainat J; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, USA.
  • Zalevsky A; Joint Research Unit for Infectious Diseases and Vectors Ecology Genetics Evolution and Control (MIVEGEC), University of Montpellier, French National Center for Scientific Research (CNRS 5290), French National Research Institute for Sustainable Development (IRD 224), 911 Avenue Agropolis, BP 64501, 3
  • Sali A; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, USA.
  • Brand CM; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, USA.
  • Wolfreys FD; Department of Pharmaceutical Chemistry, University of California, San Francisco, CA, USA.
  • Yang J; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, US.
  • Gestwicki JE; Bakar Computational Health Sciences Institute, University of California, San Francisco, CA, USA.
  • Capra JA; Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA.
  • Artursson P; Department of Ophthalmology, University of California, San Francisco, CA, USA.
  • Newman JW; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, USA.
  • Marquès-Bonet T; Department of Pharmaceutical Chemistry, University of California, San Francisco, CA, USA.
  • Giacomini KM; Institute for Neurodegenerative Diseases, University of California, San Francisco, CA, USA.
Nat Commun ; 15(1): 4380, 2024 May 23.
Article en En | MEDLINE | ID: mdl-38782905
ABSTRACT
SLC22A10 is an orphan transporter with unknown substrates and function. The goal of this study is to elucidate its substrate specificity and functional characteristics. In contrast to orthologs from great apes, human SLC22A10, tagged with green fluorescent protein, is not expressed on the plasma membrane. Cells expressing great ape SLC22A10 orthologs exhibit significant accumulation of estradiol-17ß-glucuronide, unlike those expressing human SLC22A10. Sequence alignments reveal a proline at position 220 in humans, which is a leucine in great apes. Replacing proline with leucine in SLC22A10-P220L restores plasma membrane localization and uptake function. Neanderthal and Denisovan genomes show proline at position 220, akin to modern humans, indicating functional loss during hominin evolution. Human SLC22A10 is a unitary pseudogene due to a fixed missense mutation, P220, while in great apes, its orthologs transport sex steroid conjugates. Characterizing SLC22A10 across species sheds light on its biological role, influencing organism development and steroid homeostasis.
Asunto(s)

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Primates Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Primates Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos