Regulation Of Renal Organic AnionTransporter 3 (SLC22A8) Expression And Function By The Integrity Of Lipid Raft Domains And Their Associated Cytoskeleton

ASU Author/Contributor (non-ASU co-authors, if there are any, appear on document)
Jennifer Cecile Ph.D, Assistant Professor (Creator)
Appalachian State University (ASU )
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Abstract: Background/Aims: In humans and rodents, organic anion transporter 3 (Oat3) is highlyexpressed on the basolateral membrane of renal proximal tubules and mediates the secretionof exogenous and endogenous anions. Regulation of Oat3 expression and function hasbeen observed in both expression system and intact renal epithelia. However, informationon the local membrane environment of Oat3 and its role is limited. Lipid raft domains (LRD;cholesterol-rich domains of the plasma membrane) play important roles in membrane proteinexpression, function and targeting. In the present study, we have examined the role of LRDrichmembranes and their associated cytoskeletal proteins on Oat3 expression and function.Methods: LRD-rich membranes were isolated from rat renal cortical tissues and from HEK-293cells stably expressing human OAT3 (hOAT3) by differential centrifugation with triton X-100extraction. Western blots were subsequently analyzed to determine protein expression. Inaddition, the effect of disruption of LRD-rich membranes was examined on functional Oat3mediated estrone sulfate (ES) transport in rat renal cortical slices. Cytoskeleton disruptorswere investigated in both hOAT3 expressing HEK-293 cells and rat renal cortical slices. Results:Lipid-enriched membranes from rat renal cortical tissues and hOAT3-expressing HEK-293 cellsshowed co-expression of rOat3/hOAT3 and several lipid raft-associated proteins, specificallycaveolin 1 (Cav1), ß-actin and myosin. Moreover, immunohistochemistry in hOAT3-expressingHEK-293 cells demonstrated that these LRD-rich proteins co-localized with hOAT3. Potassiumiodide (KI), an inhibitor of protein-cytoskeletal interaction, effectively detached cytoskeletonproteins and hOAT3 from plasma membrane, leading to redistribution of hOAT3 into non-LRDrichcompartments. In addition, inhibition of cytoskeleton integrity and membrane trafficking

Additional Information

Chutima Srimaroeng, Jennifer Perry Cecile, Ramsey Walden, John B. Pritchard (2013) "Regulation Of Renal Organic AnionTransporter 3 (SLC22A8) Expression And Function By The Integrity Of Lipid Raft Domains And Their Associated Cytoskeleton." Cellular Physiology and Biochemistry (open access) [DOI:10.1159/000350077] Version Of Record Available At
Language: English
Date: 2013
, renal, organic anion transporter, lipid rafts, regulation, transporters, cytoskeleton,

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