Illuminating the function of the orphan transporter, SLC22A10, in humans and other primates-Reference-Cited by-同舟云学术

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

Published:2024-05-23 Issue:1 Volume:15 Page:
ISSN:2041-1723
Container-title:Nature Communications
language:en
Short-container-title:Nat Commun

Author:

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

Abstract

AbstractSLC22A10 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.

Funder

U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences

U.S. Department of Health & Human Services | NIH | National Eye Institute

Publisher

Springer Science and Business Media LLC

Link

https://www.nature.com/articles/s41467-024-48569-7.pdf

Reference80 articles.

1. Meixner, E. et al. A substrate-based ontology for human solute carriers. Mol. Syst. Biol. 16, e9652 (2020).

2. Yee, S. W. et al. Deorphaning a solute carrier 22 family member, SLC22A15, through functional genomic studies. FASEB J. 34, 15734–15752 (2020).

3. Yee, S. W. et al. Unraveling the functional role of the orphan solute carrier, SLC22A24 in the transport of steroid conjugates through metabolomic and genome-wide association studies. PLoS Genet. 15, e1008208 (2019).

4. Girardi, E. et al. Epistasis-driven identification of SLC25A51 as a regulator of human mitochondrial NAD import. Nat. Commun. 11, 6145 (2020).

5. Higuchi, K., Sugiyama, K., Tomabechi, R., Kishimoto, H. & Inoue, K. Mammalian monocarboxylate transporter 7 (MCT7/Slc16a6) is a novel facilitative taurine transporter. J. Biol. Chem. 298, 101800 (2022).