Functional Reconstitution of Human OATP1B1 and OATP1B3 in Proteoliposomes: Effect of Bicarbonate Gradients and Substrate-specific Stimulation on Transport

An outwardly directed bicarbonate gradient drives concentrative substrate uptake by human OATP1B1 and OATP1B3 in reconstituted proteoliposomes, and His115 is required for coupling.

• Why it matters: The thermodynamic driving force for OATP1B1/OATP1B3 transport has been debated because cellular systems are complex and hard to interpret.
• What they did: The authors reconstituted isolated human OATP1B1 and OATP1B3 in proteoliposomes and used functional assays with real-time counter-ion tracking, plus ABCG2-OATP1B1 co-reconstitution and targeted mutagenesis of TM3 His115.
• The result: They found no evidence that reduced glutathione efflux provides the driving force, and they showed EGCG stimulation of OATP1B3 is intrinsic, substrate specific, and independent of other cellular proteins.

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