SLC22, SLC44, and SLC47 Transporters-Organic Anion and Cation Transporters

Molecular and Cellular Properties

Ryan M. Pelis, Stephen Wright

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Transporters within the SLC22, SLC44, and SLC47 families of solute carriers mediate transport of a structurally diverse array of organic electrolytes, that is, molecules that are generally charged (cationic, anionic, or zwitterionic) at physiological pH. Transporters in the SLC22 family-all of which are members of the major facilitator superfamily (MFS) of transporters-represent a mechanistically diverse set of processes, including the organic anion transporters (OATs and URAT1) that physiologically operate as organic anion (OA) exchangers, the organic cation transporters (OCTs) that operate as electrogenic uniporters of organic cations (OCs), and the so-called "novel" organic cation transporters (OCTNs) that support Na-cotransport of selected zwitterions. Whereas the OCTNs display a high degree of substrate selectivity, the physiological hallmark of the OATs and OCTs is their multiselectivity-consistent with a principal role in renal and hepatic clearance of a wide array of both endogenous and xenobiotic compounds. SLC47 consists of members of the multidrug and toxin extruder (MATE) family, which are carriers that are obligatory exchangers and that physiologically support electroneutral H+ exchange. The MATEs also display a characteristic multiselectivity and are frequently paired with OCTs to mediate transepithelial OC secretion, with the OCTs typically supporting basolateral OC entry and the MATEs supporting apical OC efflux. The SLC44 family contains the choline transporter-like (CTL) transporters. Largely restricted to choline and a limited set of structural congeners, the CTLs appear to support the Na-independent, electrogenic uniport of choline, thereby providing choline for membrane biogenesis. The solution of X-ray crystal structures of representative prokaryotic MFS and MATE transporters has led to the development of homology models of mammalian OAT, OCT, and MATE transporters that, in turn, have supplemented studies of the molecular basis of the complex interactions of ligands with these multiselective proteins.

Original languageEnglish (US)
Pages (from-to)233-261
Number of pages29
JournalCurrent Topics in Membranes
Volume73
DOIs
StatePublished - 2014

Fingerprint

Organic Anion Transporters
Cations
Choline
Ion Transport
Xenobiotics
Electrolytes
Anions

Keywords

  • Counter transport
  • Exchange
  • Kidney
  • Liver
  • MATE
  • OAT
  • OCT
  • Organic anion
  • Organic cation
  • Proximal tubule
  • Transport

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Cite this

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title = "SLC22, SLC44, and SLC47 Transporters-Organic Anion and Cation Transporters: Molecular and Cellular Properties",
abstract = "Transporters within the SLC22, SLC44, and SLC47 families of solute carriers mediate transport of a structurally diverse array of organic electrolytes, that is, molecules that are generally charged (cationic, anionic, or zwitterionic) at physiological pH. Transporters in the SLC22 family-all of which are members of the major facilitator superfamily (MFS) of transporters-represent a mechanistically diverse set of processes, including the organic anion transporters (OATs and URAT1) that physiologically operate as organic anion (OA) exchangers, the organic cation transporters (OCTs) that operate as electrogenic uniporters of organic cations (OCs), and the so-called {"}novel{"} organic cation transporters (OCTNs) that support Na-cotransport of selected zwitterions. Whereas the OCTNs display a high degree of substrate selectivity, the physiological hallmark of the OATs and OCTs is their multiselectivity-consistent with a principal role in renal and hepatic clearance of a wide array of both endogenous and xenobiotic compounds. SLC47 consists of members of the multidrug and toxin extruder (MATE) family, which are carriers that are obligatory exchangers and that physiologically support electroneutral H+ exchange. The MATEs also display a characteristic multiselectivity and are frequently paired with OCTs to mediate transepithelial OC secretion, with the OCTs typically supporting basolateral OC entry and the MATEs supporting apical OC efflux. The SLC44 family contains the choline transporter-like (CTL) transporters. Largely restricted to choline and a limited set of structural congeners, the CTLs appear to support the Na-independent, electrogenic uniport of choline, thereby providing choline for membrane biogenesis. The solution of X-ray crystal structures of representative prokaryotic MFS and MATE transporters has led to the development of homology models of mammalian OAT, OCT, and MATE transporters that, in turn, have supplemented studies of the molecular basis of the complex interactions of ligands with these multiselective proteins.",
keywords = "Counter transport, Exchange, Kidney, Liver, MATE, OAT, OCT, Organic anion, Organic cation, Proximal tubule, Transport",
author = "Pelis, {Ryan M.} and Stephen Wright",
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T1 - SLC22, SLC44, and SLC47 Transporters-Organic Anion and Cation Transporters

T2 - Molecular and Cellular Properties

AU - Pelis, Ryan M.

AU - Wright, Stephen

PY - 2014

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N2 - Transporters within the SLC22, SLC44, and SLC47 families of solute carriers mediate transport of a structurally diverse array of organic electrolytes, that is, molecules that are generally charged (cationic, anionic, or zwitterionic) at physiological pH. Transporters in the SLC22 family-all of which are members of the major facilitator superfamily (MFS) of transporters-represent a mechanistically diverse set of processes, including the organic anion transporters (OATs and URAT1) that physiologically operate as organic anion (OA) exchangers, the organic cation transporters (OCTs) that operate as electrogenic uniporters of organic cations (OCs), and the so-called "novel" organic cation transporters (OCTNs) that support Na-cotransport of selected zwitterions. Whereas the OCTNs display a high degree of substrate selectivity, the physiological hallmark of the OATs and OCTs is their multiselectivity-consistent with a principal role in renal and hepatic clearance of a wide array of both endogenous and xenobiotic compounds. SLC47 consists of members of the multidrug and toxin extruder (MATE) family, which are carriers that are obligatory exchangers and that physiologically support electroneutral H+ exchange. The MATEs also display a characteristic multiselectivity and are frequently paired with OCTs to mediate transepithelial OC secretion, with the OCTs typically supporting basolateral OC entry and the MATEs supporting apical OC efflux. The SLC44 family contains the choline transporter-like (CTL) transporters. Largely restricted to choline and a limited set of structural congeners, the CTLs appear to support the Na-independent, electrogenic uniport of choline, thereby providing choline for membrane biogenesis. The solution of X-ray crystal structures of representative prokaryotic MFS and MATE transporters has led to the development of homology models of mammalian OAT, OCT, and MATE transporters that, in turn, have supplemented studies of the molecular basis of the complex interactions of ligands with these multiselective proteins.

AB - Transporters within the SLC22, SLC44, and SLC47 families of solute carriers mediate transport of a structurally diverse array of organic electrolytes, that is, molecules that are generally charged (cationic, anionic, or zwitterionic) at physiological pH. Transporters in the SLC22 family-all of which are members of the major facilitator superfamily (MFS) of transporters-represent a mechanistically diverse set of processes, including the organic anion transporters (OATs and URAT1) that physiologically operate as organic anion (OA) exchangers, the organic cation transporters (OCTs) that operate as electrogenic uniporters of organic cations (OCs), and the so-called "novel" organic cation transporters (OCTNs) that support Na-cotransport of selected zwitterions. Whereas the OCTNs display a high degree of substrate selectivity, the physiological hallmark of the OATs and OCTs is their multiselectivity-consistent with a principal role in renal and hepatic clearance of a wide array of both endogenous and xenobiotic compounds. SLC47 consists of members of the multidrug and toxin extruder (MATE) family, which are carriers that are obligatory exchangers and that physiologically support electroneutral H+ exchange. The MATEs also display a characteristic multiselectivity and are frequently paired with OCTs to mediate transepithelial OC secretion, with the OCTs typically supporting basolateral OC entry and the MATEs supporting apical OC efflux. The SLC44 family contains the choline transporter-like (CTL) transporters. Largely restricted to choline and a limited set of structural congeners, the CTLs appear to support the Na-independent, electrogenic uniport of choline, thereby providing choline for membrane biogenesis. The solution of X-ray crystal structures of representative prokaryotic MFS and MATE transporters has led to the development of homology models of mammalian OAT, OCT, and MATE transporters that, in turn, have supplemented studies of the molecular basis of the complex interactions of ligands with these multiselective proteins.

KW - Counter transport

KW - Exchange

KW - Kidney

KW - Liver

KW - MATE

KW - OAT

KW - OCT

KW - Organic anion

KW - Organic cation

KW - Proximal tubule

KW - Transport

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EP - 261

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