Regulation of organic anion transporter 3 (OAT3) expression and function by membrane lipid raft‐associated proteins and cytoskeletons

Abstract

In humans and rodents, two organic anion transporters (OATs), OATs 1 and 3, are expressed on the basolateral membrane of renal proximal tubules and mediate the secretion of exogenous or endogenous anions. Regulation of OAT1 and 3 has been reported in intact renal epithelia. For example, PKC activation inhibits organic anion uptake and EGF stimulates organic anion uptake mediated by OAT1 or OAT3. However, molecular mechanisms that regulate OAT expression and function are poorly understood. In the present study, plasma membrane lipid raft domains (LRDs) involved in protein trafficking and control of membrane processes were isolated from rat renal cortex and from HEK-293, human kidney epithelial cell line. Results indicate LRDs from rat renal cortical tissues contain caveolin 1, lipid-associated protein, and myosin – components previously implicated in protein sorting, trafficking, and cell signaling cascades. Similarly, LRDs from HEK-293 cells stably expressing human OAT3 (hOAT3) show co-localization of myosin and caveolin 1 with hOAT3. Cytoskeletal disruptors also alter hOAT3 expression and transport in HEK-293 cells, while a cholesterol depleting agent reduces OAT3 transport in rat renal slices. Thus, OAT3 expression and function may be regulated by LRDs and cytoskeletons. This research was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences.