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Article

Drosophila SLC22 Orthologs Related to OATs, OCTs, and OCTNs Regulate Development and Responsiveness to Oxidative Stress

by
Darcy C. Engelhart
1,
Priti Azad
2,
Suwayda Ali
2,
Jeffry C. Granados
3,
Gabriel G. Haddad
2 and
Sanjay K. Nigam
2,4,*
1
Department of Biology, University of California San Diego, San Diego, CA 92093, USA
2
Department of Pediatrics, University of California San Diego, San Diego, CA 92093, USA
3
Department of Bioengineering, University of California San Diego, San Diego, CA 92093, USA
4
Department of Medicine, University of California San Diego, San Diego, CA 92093, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(6), 2002; https://doi.org/10.3390/ijms21062002
Submission received: 11 February 2020 / Revised: 11 March 2020 / Accepted: 13 March 2020 / Published: 15 March 2020
(This article belongs to the Special Issue Physiology, Biochemistry, and Pharmacology of Transporters for Organic Cations)
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Abstract

The SLC22 family of transporters is widely expressed, evolutionarily conserved, and plays a major role in regulating homeostasis by transporting small organic molecules such as metabolites, signaling molecules, and antioxidants. Analysis of transporters in fruit flies provides a simple yet orthologous platform to study the endogenous function of drug transporters in vivo. Evolutionary analysis of Drosophila melanogaster putative SLC22 orthologs reveals that, while many of the 25 SLC22 fruit fly orthologs do not fall within previously established SLC22 subclades, at least four members appear orthologous to mammalian SLC22 members (SLC22A16:CG6356, SLC22A15:CG7458, CG7442 and SLC22A18:CG3168). We functionally evaluated the role of SLC22 transporters in Drosophila melanogaster by knocking down 14 of these genes. Three putative SLC22 ortholog knockdowns—CG3168, CG6356, and CG7442/SLC22A—did not undergo eclosion and were lethal at the pupa stage, indicating the developmental importance of these genes. Additionally, knocking down four SLC22 members increased resistance to oxidative stress via paraquat testing (CG4630: p < 0.05, CG6006: p < 0.05, CG6126: p < 0.01 and CG16727: p < 0.05). Consistent with recent evidence that SLC22 is central to a Remote Sensing and Signaling Network (RSSN) involved in signaling and metabolism, these phenotypes support a key role for SLC22 in handling reactive oxygen species.
Keywords: solute carrier 22 (SLC22); Remote Sensing and Signaling Theory; interorgan communication; organic anion transporter; organic cation transporter; SLC22A15; SLC22A16; SLC22A18; kidney; Malpighian tubule solute carrier 22 (SLC22); Remote Sensing and Signaling Theory; interorgan communication; organic anion transporter; organic cation transporter; SLC22A15; SLC22A16; SLC22A18; kidney; Malpighian tubule

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MDPI and ACS Style

Engelhart, D.C.; Azad, P.; Ali, S.; Granados, J.C.; Haddad, G.G.; Nigam, S.K. Drosophila SLC22 Orthologs Related to OATs, OCTs, and OCTNs Regulate Development and Responsiveness to Oxidative Stress. Int. J. Mol. Sci. 2020, 21, 2002. https://doi.org/10.3390/ijms21062002

AMA Style

Engelhart DC, Azad P, Ali S, Granados JC, Haddad GG, Nigam SK. Drosophila SLC22 Orthologs Related to OATs, OCTs, and OCTNs Regulate Development and Responsiveness to Oxidative Stress. International Journal of Molecular Sciences. 2020; 21(6):2002. https://doi.org/10.3390/ijms21062002

Chicago/Turabian Style

Engelhart, Darcy C., Priti Azad, Suwayda Ali, Jeffry C. Granados, Gabriel G. Haddad, and Sanjay K. Nigam. 2020. "Drosophila SLC22 Orthologs Related to OATs, OCTs, and OCTNs Regulate Development and Responsiveness to Oxidative Stress" International Journal of Molecular Sciences 21, no. 6: 2002. https://doi.org/10.3390/ijms21062002

APA Style

Engelhart, D. C., Azad, P., Ali, S., Granados, J. C., Haddad, G. G., & Nigam, S. K. (2020). Drosophila SLC22 Orthologs Related to OATs, OCTs, and OCTNs Regulate Development and Responsiveness to Oxidative Stress. International Journal of Molecular Sciences, 21(6), 2002. https://doi.org/10.3390/ijms21062002

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