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

Author

Listed:
  • Sook Wah Yee

    (University of California)

  • Luis Ferrández-Peral

    (Dr. Aiguader 88)

  • Pol Alentorn-Moron

    (Dr. Aiguader 88)

  • Claudia Fontsere

    (Dr. Aiguader 88
    Øster Farimagsgade 5A)

  • Merve Ceylan

    (Uppsala University)

  • Megan L. Koleske

    (University of California)

  • Niklas Handin

    (Uppsala University)

  • Virginia M. Artegoitia

    (Western Human Nutrition Research Center)

  • Giovanni Lara

    (University of California)

  • Huan-Chieh Chien

    (University of California)

  • Xujia Zhou

    (University of California)

  • Jacques Dainat

    (BP 64501)

  • Arthur Zalevsky

    (University of California)

  • Andrej Sali

    (University of California
    University of California
    San Francisco)

  • Colin M. Brand

    (University of California
    University of California)

  • Finn D. Wolfreys

    (University of California)

  • Jia Yang

    (University of California)

  • Jason E. Gestwicki

    (University of California
    University of California)

  • John A. Capra

    (University of California
    University of California
    University of California
    University of California San Francisco)

  • Per Artursson

    (Uppsala University
    Uppsala University)

  • John W. Newman

    (Western Human Nutrition Research Center
    Davis)

  • Tomàs Marquès-Bonet

    (Dr. Aiguader 88
    Baldiri i Reixac 4
    c/ Columnes s/n)

  • Kathleen M. Giacomini

    (University of California
    University of California San Francisco)

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.

Suggested Citation

  • 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 &, 2024. "Illuminating the function of the orphan transporter, SLC22A10, in humans and other primates," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48569-7
    DOI: 10.1038/s41467-024-48569-7
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