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Transportomics: screening for substrates of ABC transporters in body fluids using vesicular transport assays.

By P Krumpochova, S. Sapthu, J.F.H.M. Brouwers, M. de Haas, R. de Vos, P. Borst and K. van de Wetering


ABSTRACT The ATP-binding cassette (ABC) genes encode the largest family of transmembrane proteins. ABC transporters translocate a wide variety of substrates across membranes, but their physiological function is often incompletely understood. We describe a new method to study the substrate spectrum of ABC transporters: We incubate extracts of mouse urine with membrane vesicles prepared from Spodoptera frugiperda Sf9 insect cells overproducing an ABC transporter and determine the compounds transported into the vesicles by LC/MS-based metabolomics. We illustrate the power of this simple “transportomics” approach using ABCC2, a protein present at sites of uptake and elimination. We identified many new substrates of ABCC2 in urine. These included glucuronides of plant-derived xenobiotics, a class of compounds to which humans are exposed on a daily basis. Moreover, we show that the excretion of these compounds in vivo depends on ABCC2: compared to wildtype mice, the urinary excretion of several glucuronides was increased up to 20-fold in Abcc2 / mice. Transportomics has broad applicability, as it is not restricted to urine and can be applied to other ATP-dependent transport proteins as well

Topics: International (English)
Year: 2013
OAI identifier: oai:dspace.library.uu.nl:1874/276729
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