Identification of multidrug and toxin extrusion (MATE1 and MATE2-K) variants with complete loss of transport activity
Moto Kajiwara1, Tomohiro Terada, Ken Ogasawara
1Department of Pharmacy, Kyoto University Hospital, Sakyo-ku, Kyoto, Japan.
Abstract:
H(+)/organic cation antiporters (multidrug and toxin extrusion: MATE1 and MATE2-K) play important roles in the renal tubular secretion of cationic drugs. We have recently identified a regulatory single nucleotide polymorphism (SNP) of the MATE1 gene (-32G>A). There is no other information about SNPs of the MATE gene. In this study, we evaluated the functional significance of genetic polymorphisms in MATE1 and MATE2-K. We sequenced all exons of MATE1 and MATE2-K genes in 89 Japanese subjects and identified coding SNPs (cSNPs) encoding MATE1 (V10L, G64D, A310V, D328A and N474S) and MATE2-K (K64N and G211V). All the variants except for MATE1 V10L showed significant decrease in transport activity. In particular, MATE1 G64D and MATE2-K G211V variants completely lost transport activities. When membrane expression level was evaluated by cell surface biotinylation, those of MATE1 (G64D and D328A) and MATE2-K (K64N and G211V) were significantly decreased compared with that of wild type. These findings suggested that the loss of transport activities of the MATE1 G64D and MATE2-K G211V variants were due to the alteration of protein expression in cell surface membranes. This is the first demonstration of functional impairment of the MATE family induced by cSNPs.
More Related Videos
10:43Expression, Detergent Solubilization, and Purification of a Membrane Transporter, the MexB Multidrug Resistance Protein
Published on: December 3, 2010
13:16Characterization of Membrane Transporters by Heterologous Expression in E. coli and Production of Membrane Vesicles
Published on: December 31, 2019
Related Concept Videos
ABC Transporters: Exporter
Carrier-Mediated Transport
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters
The Significance of Membrane Transport
Transporters facilitate either an active or passive movement of solutes. They can allow a single-molecule transport down its...
Membrane Transporters
Transporters are mainly composed of alpha-helices, built from bundles of ten or more helices traversing the plasma membrane. The solute-binding sites are located midway, where some of the helices are broken or distorted, making space for the binding site through...
ABC Transporters: Importer
In bacteria, based on the number of transmembrane helices and the chemical nature of their substrates, the ABC importers can be divided into three types:
