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

Abstract

ABC transporters 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 analyzed 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 and control livers have quite different ABCtransporter profiles. We propose that meaningful biological information can be derived from a direct comparison of these datasets.

Current State of SLC and ABC Transporters in the Skin and Their Relation to Sweat Metabolites and Skin Diseases

“…Such analysis has been recently reported in a study where 32 ABC transporters across five tissues have been quantified [38]. Some of the sample preparation techniques include incubation in lysis buffer, homogenization, filtration, digestion, and sometimes enrichment [38,43]. Sample preparation plays an important role in the detection of these membrane proteins.…”

“…ABC transporters found in the skin also share high homology (e.g., ABCB1, ABCB4, ABCB11, ABCA1, and ABCA2), and therefore, when analyzing these proteins, adjustments in the data analysis are necessary. For example, when publishing data sets, it is relevant to report the total intensities of unique peptides across all samples [38] along with the intensities of the shared peptides assigned according to the general ratio of the uniquely observed peptide intensities. Such analysis has been recently reported in a study where 32 ABC transporters across five tissues have been quantified [38].…”

“…For example, when publishing data sets, it is relevant to report the total intensities of unique peptides across all samples [38] along with the intensities of the shared peptides assigned according to the general ratio of the uniquely observed peptide intensities. Such analysis has been recently reported in a study where 32 ABC transporters across five tissues have been quantified [38]. Some of the sample preparation techniques include incubation in lysis buffer, homogenization, filtration, digestion, and sometimes enrichment [38,43].…”

“…A list of sweat metabolites was obtained from the human metabolome database (https://hmdb.ca/downloads accessed on 15 March 2021) [34]. Interestingly, very little evidence is available on the expression of different ABC and SLC transporters in the skin [35][36][37][38], and a thorough investigation is urgently needed to gain deeper insights into the role of SLC and ABC transporters in the skin and their relation to metabolites in sweat.…”

The incredible diversity of structures and functions of ABC transporters

“…As this special issue highlights, ABC transporters handle a wide range of structurally dissimilar endo‐ and xenobiotics in the human body, especially in tissue barriers and metabolizing or secretory organs [18–21]. If integration of molecular details into a physiological context is indeed possible, our grasp on the structure and function of ABCs should lead to clinically relevant insights.…”