The multidrug transporter MATE1 sequesters OCs within an intracellular compartment that has no influence on OC secretion in renal proximal tubules

L. J. Martínez-Guerrero, K. K. Evans, William H Dantzler, Stephen Wright

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2 Citations (Scopus)

Abstract

Secretion of organic cations (OCs) across renal proximal tubules (RPTs) involves basolateral OC transporter (OCT)2-mediated uptake from the blood followed by apical multidrug and toxin extruder (MATE)1/2- mediated efflux into the tubule filtrate. Whereas OCT2 supports electrogenic OC uniport, MATE is an OC/H+ exchanger. As assessed by epifluorescence microscopy, cultured Chinese hamster ovary (CHO) cells that stably expressed human MATE1 accumulated the fluorescent OC N,N,N-trimethyl-2-[methyl(7- nitrobenzo[c][l,2,5]oxadiazol-4-yl)amino]ethanaminium (NBDMTMA) in the cytoplasm and in a smaller, punctate compartment; accumulation in human OCT2-expressing cells was largely restricted to the cytoplasm. A second intracellular compartment was also evident in the multicompartmental kinetics of efflux of the prototypic OC [3H]1-methyl-4-phenylpyridinium (MPP) from MATE1-expressing CHO cells. Punctate accumulation of NBD-MTMA was markedly reduced by coexposure of MATE1-expressing cells with 5 μM bafilomycin (BAF), an inhibitor of V-type H+-ATPase, and accumulation of [3H]MPP and [3H]NBD-MTMA was reduced by >0% by coexposure with 5 μM BAF. BAF had no effect on the initial rate of MATE1-mediated uptake of NBD-MTMA, suggesting that the influence of BAF was a secondary effect involving inhibition of V-type H+-ATPase. The accumulation of [3H]MPP by isolated single nonperfused rabbit RPTs was also reduced > 30% by coexposure to 5 μM BAF, suggesting that the native expression in RPTs of MATE protein within endosomes can increase steady-state OC accumulation. However, the rate of [3H]MPP secretion by isolated single perfused rabbit RPTs was not affected by 5 μM BAF, suggesting that vesicles loaded with OCs+ are not likely to recycle into the apical plasma membrane at a rate sufficient to provide a parallel pathway for OC secretion.

Original languageEnglish (US)
Pages (from-to)F57-F67
JournalAmerican Journal of Physiology - Renal Physiology
Volume310
Issue number1
DOIs
StatePublished - 2015

Fingerprint

Proximal Kidney Tubule
Cations
Vacuolar Proton-Translocating ATPases
Proton-Translocating ATPases
Cricetulus
Ovary
Cytoplasm
1-Methyl-4-phenylpyridinium
Rabbits
Endosomes
Ion Transport
Microscopy
Cell Membrane
N,N,N-trimethyl-2-(methyl(7-nitrobenzo(c)(l,2,5)oxadiazol-4-yl)amino)ethanaminium

Keywords

  • Multidrug and toxin extruder 1
  • Organic cation secretion
  • Proximal tubule
  • Transport

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

@article{cd1f55fcad9c40fd907d492222ea1163,
title = "The multidrug transporter MATE1 sequesters OCs within an intracellular compartment that has no influence on OC secretion in renal proximal tubules",
abstract = "Secretion of organic cations (OCs) across renal proximal tubules (RPTs) involves basolateral OC transporter (OCT)2-mediated uptake from the blood followed by apical multidrug and toxin extruder (MATE)1/2- mediated efflux into the tubule filtrate. Whereas OCT2 supports electrogenic OC uniport, MATE is an OC/H+ exchanger. As assessed by epifluorescence microscopy, cultured Chinese hamster ovary (CHO) cells that stably expressed human MATE1 accumulated the fluorescent OC N,N,N-trimethyl-2-[methyl(7- nitrobenzo[c][l,2,5]oxadiazol-4-yl)amino]ethanaminium (NBDMTMA) in the cytoplasm and in a smaller, punctate compartment; accumulation in human OCT2-expressing cells was largely restricted to the cytoplasm. A second intracellular compartment was also evident in the multicompartmental kinetics of efflux of the prototypic OC [3H]1-methyl-4-phenylpyridinium (MPP) from MATE1-expressing CHO cells. Punctate accumulation of NBD-MTMA was markedly reduced by coexposure of MATE1-expressing cells with 5 μM bafilomycin (BAF), an inhibitor of V-type H+-ATPase, and accumulation of [3H]MPP and [3H]NBD-MTMA was reduced by >0{\%} by coexposure with 5 μM BAF. BAF had no effect on the initial rate of MATE1-mediated uptake of NBD-MTMA, suggesting that the influence of BAF was a secondary effect involving inhibition of V-type H+-ATPase. The accumulation of [3H]MPP by isolated single nonperfused rabbit RPTs was also reduced > 30{\%} by coexposure to 5 μM BAF, suggesting that the native expression in RPTs of MATE protein within endosomes can increase steady-state OC accumulation. However, the rate of [3H]MPP secretion by isolated single perfused rabbit RPTs was not affected by 5 μM BAF, suggesting that vesicles loaded with OCs+ are not likely to recycle into the apical plasma membrane at a rate sufficient to provide a parallel pathway for OC secretion.",
keywords = "Multidrug and toxin extruder 1, Organic cation secretion, Proximal tubule, Transport",
author = "Mart{\'i}nez-Guerrero, {L. J.} and Evans, {K. K.} and Dantzler, {William H} and Stephen Wright",
year = "2015",
doi = "10.1152/ajprenal.00318.2015",
language = "English (US)",
volume = "310",
pages = "F57--F67",
journal = "American Journal of Physiology",
issn = "0363-6143",
publisher = "American Physiological Society",
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TY - JOUR

T1 - The multidrug transporter MATE1 sequesters OCs within an intracellular compartment that has no influence on OC secretion in renal proximal tubules

AU - Martínez-Guerrero, L. J.

AU - Evans, K. K.

AU - Dantzler, William H

AU - Wright, Stephen

PY - 2015

Y1 - 2015

N2 - Secretion of organic cations (OCs) across renal proximal tubules (RPTs) involves basolateral OC transporter (OCT)2-mediated uptake from the blood followed by apical multidrug and toxin extruder (MATE)1/2- mediated efflux into the tubule filtrate. Whereas OCT2 supports electrogenic OC uniport, MATE is an OC/H+ exchanger. As assessed by epifluorescence microscopy, cultured Chinese hamster ovary (CHO) cells that stably expressed human MATE1 accumulated the fluorescent OC N,N,N-trimethyl-2-[methyl(7- nitrobenzo[c][l,2,5]oxadiazol-4-yl)amino]ethanaminium (NBDMTMA) in the cytoplasm and in a smaller, punctate compartment; accumulation in human OCT2-expressing cells was largely restricted to the cytoplasm. A second intracellular compartment was also evident in the multicompartmental kinetics of efflux of the prototypic OC [3H]1-methyl-4-phenylpyridinium (MPP) from MATE1-expressing CHO cells. Punctate accumulation of NBD-MTMA was markedly reduced by coexposure of MATE1-expressing cells with 5 μM bafilomycin (BAF), an inhibitor of V-type H+-ATPase, and accumulation of [3H]MPP and [3H]NBD-MTMA was reduced by >0% by coexposure with 5 μM BAF. BAF had no effect on the initial rate of MATE1-mediated uptake of NBD-MTMA, suggesting that the influence of BAF was a secondary effect involving inhibition of V-type H+-ATPase. The accumulation of [3H]MPP by isolated single nonperfused rabbit RPTs was also reduced > 30% by coexposure to 5 μM BAF, suggesting that the native expression in RPTs of MATE protein within endosomes can increase steady-state OC accumulation. However, the rate of [3H]MPP secretion by isolated single perfused rabbit RPTs was not affected by 5 μM BAF, suggesting that vesicles loaded with OCs+ are not likely to recycle into the apical plasma membrane at a rate sufficient to provide a parallel pathway for OC secretion.

AB - Secretion of organic cations (OCs) across renal proximal tubules (RPTs) involves basolateral OC transporter (OCT)2-mediated uptake from the blood followed by apical multidrug and toxin extruder (MATE)1/2- mediated efflux into the tubule filtrate. Whereas OCT2 supports electrogenic OC uniport, MATE is an OC/H+ exchanger. As assessed by epifluorescence microscopy, cultured Chinese hamster ovary (CHO) cells that stably expressed human MATE1 accumulated the fluorescent OC N,N,N-trimethyl-2-[methyl(7- nitrobenzo[c][l,2,5]oxadiazol-4-yl)amino]ethanaminium (NBDMTMA) in the cytoplasm and in a smaller, punctate compartment; accumulation in human OCT2-expressing cells was largely restricted to the cytoplasm. A second intracellular compartment was also evident in the multicompartmental kinetics of efflux of the prototypic OC [3H]1-methyl-4-phenylpyridinium (MPP) from MATE1-expressing CHO cells. Punctate accumulation of NBD-MTMA was markedly reduced by coexposure of MATE1-expressing cells with 5 μM bafilomycin (BAF), an inhibitor of V-type H+-ATPase, and accumulation of [3H]MPP and [3H]NBD-MTMA was reduced by >0% by coexposure with 5 μM BAF. BAF had no effect on the initial rate of MATE1-mediated uptake of NBD-MTMA, suggesting that the influence of BAF was a secondary effect involving inhibition of V-type H+-ATPase. The accumulation of [3H]MPP by isolated single nonperfused rabbit RPTs was also reduced > 30% by coexposure to 5 μM BAF, suggesting that the native expression in RPTs of MATE protein within endosomes can increase steady-state OC accumulation. However, the rate of [3H]MPP secretion by isolated single perfused rabbit RPTs was not affected by 5 μM BAF, suggesting that vesicles loaded with OCs+ are not likely to recycle into the apical plasma membrane at a rate sufficient to provide a parallel pathway for OC secretion.

KW - Multidrug and toxin extruder 1

KW - Organic cation secretion

KW - Proximal tubule

KW - Transport

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U2 - 10.1152/ajprenal.00318.2015

DO - 10.1152/ajprenal.00318.2015

M3 - Article

C2 - 26538438

AN - SCOPUS:84949549539

VL - 310

SP - F57-F67

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0363-6143

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