Next Article in Journal
Research Advances of Beneficial Microbiota Associated with Crop Plants
Next Article in Special Issue
Drosophila SLC22 Orthologs Related to OATs, OCTs, and OCTNs Regulate Development and Responsiveness to Oxidative Stress
Previous Article in Journal
Modulation of Energy Metabolism Is Important for Low-Oxygen Stress Adaptation in Brassicaceae Species
Article

Systems Biology Analysis Reveals Eight SLC22 Transporter Subgroups, Including OATs, OCTs, and OCTNs

1
Department of Biology, University of California San Diego, San Diego, CA 92093, USA
2
Department of Bioengineering, University of California San Diego, San Diego, CA 92093, USA
3
School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, San Diego, CA 92093, USA
4
Department of Molecular Biology, Division of Biological Sciences, University of California San Diego, San Diego, CA 92093, USA
5
Department of Medicine, University of California San Diego, San Diego, CA 92093, USA
6
Department of Pediatrics, University of California San Diego, San Diego, CA 92093, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(5), 1791; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21051791
Received: 11 February 2020 / Revised: 2 March 2020 / Accepted: 3 March 2020 / Published: 5 March 2020
The SLC22 family of OATs, OCTs, and OCTNs is emerging as a central hub of endogenous physiology. Despite often being referred to as “drug” transporters, they facilitate the movement of metabolites and key signaling molecules. An in-depth reanalysis supports a reassignment of these proteins into eight functional subgroups, with four new subgroups arising from the previously defined OAT subclade: OATS1 (SLC22A6, SLC22A8, and SLC22A20), OATS2 (SLC22A7), OATS3 (SLC22A11, SLC22A12, and Slc22a22), and OATS4 (SLC22A9, SLC22A10, SLC22A24, and SLC22A25). We propose merging the OCTN (SLC22A4, SLC22A5, and Slc22a21) and OCT-related (SLC22A15 and SLC22A16) subclades into the OCTN/OCTN-related subgroup. Using data from GWAS, in vivo models, and in vitro assays, we developed an SLC22 transporter-metabolite network and similar subgroup networks, which suggest how multiple SLC22 transporters with mono-, oligo-, and multi-specific substrate specificity interact to regulate metabolites. Subgroup associations include: OATS1 with signaling molecules, uremic toxins, and odorants, OATS2 with cyclic nucleotides, OATS3 with uric acid, OATS4 with conjugated sex hormones, particularly etiocholanolone glucuronide, OCT with neurotransmitters, and OCTN/OCTN-related with ergothioneine and carnitine derivatives. Our data suggest that the SLC22 family can work among itself, as well as with other ADME genes, to optimize levels of numerous metabolites and signaling molecules, involved in organ crosstalk and inter-organismal communication, as proposed by the remote sensing and signaling theory. View Full-Text
Keywords: transporters; endogenous metabolism; functional subgroups; SLC22; remote sensing and signaling; drug transporters; gut microbiome; chronic kidney disease transporters; endogenous metabolism; functional subgroups; SLC22; remote sensing and signaling; drug transporters; gut microbiome; chronic kidney disease
Show Figures

Figure 1

MDPI and ACS Style

Engelhart, D.C.; Granados, J.C.; Shi, D.; Saier Jr., M.H., Jr.; Baker, M.E.; Abagyan, R.; Nigam, S.K. Systems Biology Analysis Reveals Eight SLC22 Transporter Subgroups, Including OATs, OCTs, and OCTNs. Int. J. Mol. Sci. 2020, 21, 1791. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21051791

AMA Style

Engelhart DC, Granados JC, Shi D, Saier Jr. MH Jr., Baker ME, Abagyan R, Nigam SK. Systems Biology Analysis Reveals Eight SLC22 Transporter Subgroups, Including OATs, OCTs, and OCTNs. International Journal of Molecular Sciences. 2020; 21(5):1791. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21051791

Chicago/Turabian Style

Engelhart, Darcy C., Jeffry C. Granados, Da Shi, Milton H. Saier Jr. Jr., Michael E. Baker, Ruben Abagyan, and Sanjay K. Nigam 2020. "Systems Biology Analysis Reveals Eight SLC22 Transporter Subgroups, Including OATs, OCTs, and OCTNs" International Journal of Molecular Sciences 21, no. 5: 1791. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21051791

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop