Cloning, function, and localization of human, canine, and Drosophila ZIP10 (SLC39A10), a Zn2+ transporter

Landry, G. M. et al. (2019) Cloning, function, and localization of human, canine, and Drosophila ZIP10 (SLC39A10), a Zn2+ transporter. American Journal of Physiology: Renal Physiology, 316(2), F263-F273. (doi: 10.1152/ajprenal.00573.2017) (PMID:30520657)

Abstract

Zinc (Zn2+) is the second most abundant trace element, but is considered a micronutrient, as it is a cofactor for many enzymes and transcription factors. Whereas Zn2+ deficiency can cause cognitive immune or metabolic dysfunction and infertility, excess Zn2+ is nephrotoxic. As for other ions and solutes, Zn2+ is moved into and out of cells by specific membrane transporters: ZnT, Zip, and NRAMP/DMT proteins. ZIP10 is reported to be localized at the apical membrane of renal proximal tubules in rats, where it is believed to play a role in Zn2+ import. Renal regulation of Zn2+ is of particular interest in light of growing evidence that Zn2+ may play a role in kidney stone formation. The objective of this study was to show that ZIP10 homologs transport Zn2+, as well as ZIP10, kidney localization across species. We cloned ZIP10 from dog, human, and Drosophila (CG10006), tested clones for Zn2+ uptake in Xenopus oocytes and localized the protein in renal structures. CG10006, rather than foi (fear-of-intimacy, CG6817) is the primary ZIP10 homolog found in Drosophila Malpighian tubules. The ZIP10 antibody recognizes recombinant dog, human, and Drosophila ZIP10 proteins. Immunohistochemistry reveals that ZIP10 in higher mammals is found not only in the proximal tubule, but also in the collecting duct system. These ZIP10 proteins show Zn2+ transport. Together, these studies reveal ZIP10 kidney localization, a role in renal Zn2+ transport, and indicates that CG10006 is a Drosophila homolog of ZIP10.

• Item Type: Articles
• Additional Information: This work was supported by National Institute of Diabetes and Digestive and Kidney Diseases Grants DK-092408, U54-DK100227 (O’Brien Urology Research Center), and R25-DK-101405, and a grant from the Oxalosis and Hyperoxaluria Foundation. G. M. Landry was supported by Grant T32-DK007013.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Cabrero, Mr Pablo and Dow, Professor Julian
• Authors: Landry, G. M., Furrow, E., Holmes, H. L., Hirata, T., Kato, A., Williams, P., Strohmaier, K., Gallo, C. J. R., Chang, M., Pandey, M. K., Jiang, H., Bansal, A., Franz, M.-C., Montalbetti, N., Alexander, M. P., Cabrero, P., Dow, J. A.T., DeGrado, T. R., and Romero, M. F.
• College/School: College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
• Journal Name: American Journal of Physiology: Renal Physiology
• Publisher: American Physiological Society
• ISSN: 1931-857X
• ISSN (Online): 1522-1466
• Published Online: 06 December 2018
• Copyright Holders: Copyright © 2019 American Physiological Society
• First Published: First published in American Journal of Physiology: Renal Physiology 316(2): F263-F273
• Publisher Policy: Reproduced in accordance with the publisher copyright policy