Mass spectrometry-based abundance atlas of ABC transporters in human liver, gut, kidney, brain and skin

FEBS Lett. 2020 Dec;594(23):4134-4150. doi: 10.1002/1873-3468.13982. Epub 2020 Dec 3.

Abstract

ABC transporters (ATP-binding cassette transporter) traffic drugs and their metabolites across membranes, making ABC transporter expression levels a key factor regulating local drug concentrations in different tissues and individuals. Yet, quantification of ABC transporters remains challenging because they are large and low-abundance transmembrane proteins. Here, we analysed 200 samples of crude and membrane-enriched fractions from human liver, kidney, intestine, brain microvessels and skin, by label-free quantitative mass spectrometry. We identified 32 (out of 48) ABC transporters: ABCD3 was the most abundant in liver, whereas ABCA8, ABCB2/TAP1 and ABCE1 were detected in all tissues. Interestingly, this atlas unveiled that ABCB2/TAP1 may have TAP2-independent functions in the brain and that biliary atresia (BA) and control livers have quite different ABC transporter profiles. We propose that meaningful biological information can be derived from a direct comparison of these data sets.

Keywords: ABC transporters; biliary atresia; global proteomics; human brain; human intestine; human kidney; human liver; human skin; mass spectrometry; total protein approach.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / analysis*
  • ATP-Binding Cassette Transporters / chemistry*
  • ATP-Binding Cassette Transporters / metabolism
  • Adolescent
  • Adult
  • Brain / metabolism*
  • Child
  • Child, Preschool
  • Humans
  • Infant
  • Infant, Newborn
  • Intestinal Mucosa / metabolism*
  • Kidney / metabolism*
  • Liver / metabolism*
  • Male
  • Mass Spectrometry
  • Organ Specificity
  • Skin / metabolism*

Substances

  • ATP-Binding Cassette Transporters