Illuminating the function of the orphan transporter, SLC22A10, in humans and other primates
Yee, Sook Wah (University of California. Department of Bioengineering and Therapeutic Sciences)
Ferrández-Peral, Luis (Institute of Evolutionary Biology)
Alentorn-Moron, Pol (Institute of Evolutionary Biology)
Fontsere, Claudia (University of Copenhagen)
Ceylan, Merve (Uppsala University. Department of Pharmacy)
Koleske, Megan L. (University of California. Department of Bioengineering and Therapeutic Sciences)
Handin, Niklas (Uppsala University. Department of Pharmacy)
Artegoitia, Virginia M. (Western Human Nutrition Research Center)
Lara, Giovanni (University of California. Department of Bioengineering and Therapeutic Sciences)
Chien, Huan-Chieh (University of California. Department of Bioengineering and Therapeutic Sciences)
Zhou, Xujia (University of California. Department of Bioengineering and Therapeutic Sciences)
Dainat, Jacques (University of Montpellier)
Zalevsky, Arthur (University of California. Department of Bioengineering and Therapeutic Sciences)
Sali, Andrej (University of California)
Brand, Colin M. (University of California. Department of Epidemiology and Biostatistics)
Wolfreys, Finn D. (University of California. Department of Ophthalmology)
Yang, Jia (University of California. Department of Bioengineering and Therapeutic Sciences)
Gestwicki, Jason E. (University of California. Department of Pharmaceutical Chemistry)
Capra, John A. (University of California. Department of Bioengineering and Therapeutic Sciences)
Artursson, Per (Uppsala University. Department of Pharmacy)
Newman, John W. (University of California. Department of Nutrition)
Marques-Bonet, Tomas 1975- (Institut Català de Paleontologia Miquel Crusafont)
Giacomini, Kathleen M. (University of California. Department of Bioengineering and Therapeutic Sciences)

Data:	2024
Resum:	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.
Ajuts:	European Commission 864203 Agencia Estatal de Investigación PID2021-126004NB-100 Agència de Gestió d'Ajuts Universitaris i de Recerca 2021/SGR-00177
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Open reading frames ; Evolution ; Gene expression profiling
Publicat a:	Nature communications, Vol. 15 (May 2024) , art. 4380, ISSN 2041-1723

DOI: 10.1038/s41467-024-48569-7
PMID: 38782905

17 p, 4.8 MB

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