Illuminating the function of the orphan transporter, SLC22A10, in humans and other primates

Sook Wah Yee; Luis Ferrández-Peral; Pol Alentorn-Moron; Claudia Fontsere; Merve Ceylan; Megan L. Koleske; Niklas Handin; Virginia M. Artegoitia; Giovanni Lara; Huan-Chieh Chien; Xujia Zhou; Jacques Dainat; Arthur Zalevsky; Andrej Sali; Colin M. Brand; Finn D. Wolfreys; Jia Yang; Jason E. Gestwicki; John A. Capra; Per Artursson; John W. Newman; Tomàs Marquès-Bonet; Kathleen M. Giacomini

doi:10.1038/s41467-024-48569-7

Nature Communications (May 2024)

Illuminating the function of the orphan transporter, SLC22A10, in humans and other primates

Sook Wah Yee,
Luis Ferrández-Peral,
Pol Alentorn-Moron,
Claudia Fontsere,
Merve Ceylan,
Megan L. Koleske,
Niklas Handin,
Virginia M. Artegoitia,
Giovanni Lara,
Huan-Chieh Chien,
Xujia Zhou,
Jacques Dainat,
Arthur Zalevsky,
Andrej Sali,
Colin M. Brand,
Finn D. Wolfreys,
Jia Yang,
Jason E. Gestwicki,
John A. Capra,
Per Artursson,
John W. Newman,
Tomàs Marquès-Bonet,
Kathleen M. Giacomini

Affiliations

Sook Wah Yee: Department of Bioengineering and Therapeutic Sciences, University of California
Luis Ferrández-Peral: Institute of Evolutionary Biology (UPF-CSIC), PRBB, Dr. Aiguader 88
Pol Alentorn-Moron: Institute of Evolutionary Biology (UPF-CSIC), PRBB, Dr. Aiguader 88
Claudia Fontsere: Institute of Evolutionary Biology (UPF-CSIC), PRBB, Dr. Aiguader 88
Merve Ceylan: Department of Pharmacy, Uppsala University
Megan L. Koleske: Department of Bioengineering and Therapeutic Sciences, University of California
Niklas Handin: Department of Pharmacy, Uppsala University
Virginia M. Artegoitia: United States Department of Agriculture, Agricultural Research Service, Western Human Nutrition Research Center
Giovanni Lara: Department of Bioengineering and Therapeutic Sciences, University of California
Huan-Chieh Chien: Department of Bioengineering and Therapeutic Sciences, University of California
Xujia Zhou: Department of Bioengineering and Therapeutic Sciences, University of California
Jacques Dainat: 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
Arthur Zalevsky: Department of Bioengineering and Therapeutic Sciences, University of California
Andrej Sali: Department of Bioengineering and Therapeutic Sciences, University of California
Colin M. Brand: Bakar Computational Health Sciences Institute, University of California
Finn D. Wolfreys: Department of Ophthalmology, University of California
Jia Yang: Department of Bioengineering and Therapeutic Sciences, University of California
Jason E. Gestwicki: Department of Pharmaceutical Chemistry, University of California
John A. Capra: Department of Bioengineering and Therapeutic Sciences, University of California
Per Artursson: Department of Pharmacy, Uppsala University
John W. Newman: United States Department of Agriculture, Agricultural Research Service, Western Human Nutrition Research Center
Tomàs Marquès-Bonet: Institute of Evolutionary Biology (UPF-CSIC), PRBB, Dr. Aiguader 88
Kathleen M. Giacomini: Department of Bioengineering and Therapeutic Sciences, University of California

DOI: https://doi.org/10.1038/s41467-024-48569-7
Journal volume & issue: Vol. 15, no. 1
pp. 1 – 17

Abstract

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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-17β-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.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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