Systems Biology Analysis Reveals Eight SLC22 Transporter Subgroups, Including OATs, OCTs, and OCTNs, and Drosophila SLC22 orthologs related to OATs, OCTs, and OCTNs regulate development and responsiveness to oxidative stress
- Author(s): Engelhart, Darcy
- Advisor(s): Nigam, Sanjay K
- Saier, Milton H
- et al.
The SLC22 family of transmembrane transport proteins consists of at least 31 known members that transport organic anions (OATs), organic cations (OCTs) and zwitterions (OCTNs). Despite their interaction with many endogenous metabolites and signaling molecules, many of these transporters are referred to as “drug” transporters since they facilitate the movement of pharmaceutical drugs. However, their evolution and conservation as a group underscores key endogenous functions.
Chapter 1 suggests a re-designation of SLC22 into nine subclades with four new, functional subclades arising out of the previously defined Oat subclade - referred to as Oat subgroups. These new Oat subgroups are: OATS1 (SLC22A6, SLC22A8, and SLC22A20), OATS2 (SLC22A7), OATS3 (SLC22A11, SLC22A12, and slc22a22), and OATS4 (SLC22A9, SLC22A10, SLC22A24, SLC22A25 plus the rodent expansion of slc22a19, and slc22a26-30). We also propose the reclassification of SLC22A16 into the preexisting OCTN subclade (SLC22A4, SLC22A5, and slc22a21) and the renaming of the Oct-related subclade, which now contains only SLC22A15, to the Octn-related subclade.
Due to the functional similarities between the Drosophila melanogaster (fruit fly) hindgut and Malpighian tubules and the human intestines and kidneys, where most, if not all SLC22 family members can be localized, we are assessing the functionality of SLC22 transport proteins using flies as a model organism. Chapter 2 explores orthologous relationships between D. melanogaster transporters and their human counterparts. It also assesses fly transporters for their role in management of oxidative stress.