Molecular insights into the structure-function relationship of organic anion transporters OATs.
The organic anion transporter (OAT) family encoded by SLC22A mediates the absorption, distribution, and excretion of a diverse array of environmental toxins, and clinically important drugs, including anti-HIV therapeutics, anti-tumor drugs, antibiotics, anti-hypertensives, and anti-inflammatories, and therefore is critical for the survival of mammalian species. Several OATs have been identified: OAT1 (SLC22A6), OAT2 (SLC22A7), OAT3 (SLC22A8), OAT4 (SLC22A11), OAT5 (SLC22A19) OAT6 (SLC22A20) and URAT1 (SLC22A12). The expressions of these OATs have been detected in key organs such as kidney, liver, brain and placenta. OAT dysfunction in these organs may contribute to the renal, hepatic, neurological and fetal toxicity and diseases. In this review, we summarize, according to the work done by our laboratory as well as by others, the most updated molecular studies on these OAT members, especially on the aspect of their structure-function relationships. The functional roles of N-glycosylation, transmembrane domains and individual amino acids, cell surface assembly, as well as associating proteins will be discussed. In addition, we will show the recent analyses of coding region polymorphisms of OATs, which give us information on the genetic variants of OATs and their potential effects on OAT functions.
Zhou
Fanfan
F
Department of Pharmaceutics, Rutgers, the State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ 08854, USA.
You
Guofeng
G
D000818:Animals; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D027361:Organic Anion Transporters / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011110:Polymorphism, Genetic; D013329:Structure-Activity Relationship
D027361:Organic Anion Transporters