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J Physiol
2022 May 01;60010:2377-2400. doi: 10.1113/JP282781.
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Functional characterization of Atlantic salmon (Salmo salar L.) PepT2 transporters.
Vacca F
,
Gomes AS
,
Murashita K
,
Cinquetti R
,
Roseti C
,
Barca A
,
Rønnestad I
,
Verri T
,
Bossi E
.
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The high-affinity/low-capacity system Slc15a2 (PepT2) is responsible for the reuptake of di/tripeptides from the renal proximal tubule, but it also operates in many other tissues and organs. Information regarding PepT2 in teleost fish is limited and, to date, functional data are available from the zebrafish (Danio rerio) only. Here, we report the identification of two slc15a2 genes in the Atlantic salmon (Salmo salar) genome, namely slc15a2a and slc15a2b. The two encoded PepT2 proteins share 87% identity and resemble both structurally and functionally the canonical vertebrate PepT2 system. The mRNA tissue distribution analyses reveal a widespread distribution of slc15a2a transcripts, being more abundant in the brain and gills, while slc15a2b transcripts are mainly expressed in the kidney and the distal part of the gastrointestinal tract. The function of the two transporters was investigated by heterologous expression in Xenopus laevis oocytes and two-electrode voltage-clamp recordings of transport and presteady-state currents. Both PepT2a and PepT2b in the presence of Gly-Gln elicit pH-dependent and Na+ independent inward currents. The biophysical and kinetic analysis of the recorded currents defined the transport properties, confirming that the two Atlantic salmon PepT2 proteins behave as high-affinity/low-capacity transporters. The recent structures and the previous kinetic schemes of rat and human PepT2 qualitatively account for the characteristics of the two Atlantic salmon proteins. This study is the first to report on the functional expression of two PepT2-type transporters that operate in the same vertebrate organism as a result of (a) gene duplication process(es). KEY POINTS: Two slc15a2-type genes, slc15a2a and slc15a2b coding for PepT2-type peptide transporters were found in the Atlantic salmon. slc15a2a transcripts, widely distributed in the fish tissues, are abundant in the brain and gills, while slc15a2b transcripts are mainly expressed in the kidney and distalgastrointestinal tract. Amino acids involved in vertebrate Slc15 transport function are conserved in PepT2a and PepT2b proteins. Detailed kinetic analysis indicates that both PepT2a and PepT2b operate as high-affinity transporters. The kinetic schemes and structures proposed for the mammalian models of PepT2 are suitable to explain the function of the two Atlantic salmon transporters.
Amasheh,
Electrophysiological analysis of the function of the mammalian renal peptide transporter expressed in Xenopus laevis oocytes.
1997, Pubmed,
Xenbase
Amasheh,
Electrophysiological analysis of the function of the mammalian renal peptide transporter expressed in Xenopus laevis oocytes.
1997,
Pubmed
,
Xenbase
Barat,
Solute carriers (SLCs) identified and characterized from kidney transcriptome of golden mahseer (Tor putitora) (Fam: Cyprinidae).
2016,
Pubmed
Biegel,
The renal type H+/peptide symporter PEPT2: structure-affinity relationships.
2006,
Pubmed
Boll,
Expression cloning and functional characterization of the kidney cortex high-affinity proton-coupled peptide transporter.
1996,
Pubmed
,
Xenbase
Bosdriesz,
Low affinity uniporter carrier proteins can increase net substrate uptake rate by reducing efflux.
2018,
Pubmed
Bossi,
Temperature effects on the kinetic properties of the rabbit intestinal oligopeptide cotransporter PepT1.
2012,
Pubmed
,
Xenbase
Bossi,
Exogenous protein expression in Xenopus oocytes: basic procedures.
2007,
Pubmed
,
Xenbase
Bossi,
Role of anion-cation interactions on the pre-steady-state currents of the rat Na(+)-Cl(-)-dependent GABA cotransporter rGAT1.
2002,
Pubmed
,
Xenbase
Bossi,
Residues R282 and D341 act as electrostatic gates in the proton-dependent oligopeptide transporter PepT1.
2011,
Pubmed
,
Xenbase
Buracco,
Dictyostelium Nramp1, which is structurally and functionally similar to mammalian DMT1 transporter, mediates phagosomal iron efflux.
2015,
Pubmed
,
Xenbase
Castagna,
The Lepidopteran KAAT1 and CAATCH1: Orthologs to Understand Structure-Function Relationships in Mammalian SLC6 Transporters.
2022,
Pubmed
,
Xenbase
Chen,
Stoichiometry and kinetics of the high-affinity H+-coupled peptide transporter PepT2.
1999,
Pubmed
,
Xenbase
Cherubino,
Pre-steady-state and reverse transport currents in the GABA transporter GAT1.
2012,
Pubmed
,
Xenbase
Chourasia,
Effects of the acclimation to high salinity on intestinal ion and peptide transporters in two tilapia species that differ in their salinity tolerance.
2018,
Pubmed
Con,
Salinity-Dependent Shift in the Localization of Three Peptide Transporters along the Intestine of the Mozambique Tilapia (Oreochromis mossambicus).
2017,
Pubmed
Con,
Peptide Transporters in the Primary Gastrointestinal Tract of Pre-Feeding Mozambique Tilapia Larva.
2019,
Pubmed
de Castro,
ScanProsite: detection of PROSITE signature matches and ProRule-associated functional and structural residues in proteins.
2006,
Pubmed
Delpire,
Housing and husbandry of Xenopus laevis affect the quality of oocytes for heterologous expression studies.
2011,
Pubmed
,
Xenbase
Del Vecchio,
Effects of Short-Term Fasting on mRNA Expression of Ghrelin and the Peptide Transporters PepT1 and 2 in Atlantic Salmon (Salmo salar).
2021,
Pubmed
Dong,
Phylogeny of Slc15 family and response to Aeromonas hydrophila infection following Lactococcus lactis dietary supplementation in Cyprinus carpio.
2020,
Pubmed
Döring,
Delta-aminolevulinic acid transport by intestinal and renal peptide transporters and its physiological and clinical implications.
1998,
Pubmed
,
Xenbase
Eskandari,
Thyroid Na+/I- symporter. Mechanism, stoichiometry, and specificity.
1997,
Pubmed
,
Xenbase
Fesce,
The relation between charge movement and transport-associated currents in the rat GABA cotransporter rGAT1.
2002,
Pubmed
,
Xenbase
Forlani,
Mutation K448E in the external loop 5 of rat GABA transporter rGAT1 induces pH sensitivity and alters substrate interactions.
2001,
Pubmed
,
Xenbase
Forster,
Electrogenic kinetics of a mammalian intestinal type IIb Na(+)/P(i) cotransporter.
2006,
Pubmed
,
Xenbase
Gomes,
Identification and characterization of the Atlantic salmon peptide transporter 1a.
2020,
Pubmed
,
Xenbase
Huang,
Molecular evolution of the Slc15 family and its response to waterborne copper and mercury exposure in tilapia.
2015,
Pubmed
Jones,
The rapid generation of mutation data matrices from protein sequences.
1992,
Pubmed
Jumper,
Highly accurate protein structure prediction with AlphaFold.
2021,
Pubmed
Kamal,
Role and relevance of PEPT2 in drug disposition, dynamics, and toxicity.
2008,
Pubmed
Keep,
Choroid plexus transport: gene deletion studies.
2011,
Pubmed
Killer,
Structural snapshots of human PepT1 and PepT2 reveal mechanistic insights into substrate and drug transport across epithelial membranes.
2021,
Pubmed
Kokou,
Short- and long-term low-salinity acclimation effects on the branchial and intestinal gene expression in the European seabass (Dicentrarchus labrax).
2019,
Pubmed
Kottra,
Bidirectional electrogenic transport of peptides by the proton-coupled carrier PEPT1 in Xenopus laevis oocytes: its asymmetry and symmetry.
2001,
Pubmed
,
Xenbase
Kottra,
Inhibition of intracellular dipeptide hydrolysis uncovers large outward transport currents of the peptide transporter PEPT1 in Xenopus oocytes.
2009,
Pubmed
,
Xenbase
Kottra,
PEPT1 as a paradigm for membrane carriers that mediate electrogenic bidirectional transport of anionic, cationic, and neutral substrates.
2002,
Pubmed
,
Xenbase
Kuang,
The genetic map of goldfish (Carassius auratus) provided insights to the divergent genome evolutions in the Cyprinidae family.
2016,
Pubmed
Kumar,
MEGA X: Molecular Evolutionary Genetics Analysis across Computing Platforms.
2018,
Pubmed
Lester,
Listening to neurotransmitter transporters.
1996,
Pubmed
Lien,
The Atlantic salmon genome provides insights into rediploidization.
2016,
Pubmed
Liu,
Molecular cloning of PEPT 2, a new member of the H+/peptide cotransporter family, from human kidney.
1995,
Pubmed
Loo,
Conformational changes couple Na+ and glucose transport.
1998,
Pubmed
,
Xenbase
Mackenzie,
Mechanisms of the human intestinal H+-coupled oligopeptide transporter hPEPT1.
1996,
Pubmed
,
Xenbase
Mackenzie,
Relationships between Na+/glucose cotransporter (SGLT1) currents and fluxes.
1998,
Pubmed
,
Xenbase
Macqueen,
A well-constrained estimate for the timing of the salmonid whole genome duplication reveals major decoupling from species diversification.
2014,
Pubmed
Mager,
Measurement of transient currents from neurotransmitter transporters expressed in Xenopus oocytes.
1998,
Pubmed
,
Xenbase
Mager,
Ion binding and permeation at the GABA transporter GAT1.
1996,
Pubmed
,
Xenbase
Mager,
Steady states, charge movements, and rates for a cloned GABA transporter expressed in Xenopus oocytes.
1993,
Pubmed
,
Xenbase
Margheritis,
Characterization of the transport of lysine-containing dipeptides by PepT1 orthologs expressed in Xenopus laevis oocytes.
2013,
Pubmed
,
Xenbase
McNamara,
Husbandry, General Care, and Transportation of Xenopus laevis and Xenopus tropicalis.
2018,
Pubmed
,
Xenbase
Mertl,
Substrate-induced changes in the density of peptide transporter PEPT1 expressed in Xenopus oocytes.
2008,
Pubmed
,
Xenbase
Nussberger,
Symmetry of H+ binding to the intra- and extracellular side of the H+-coupled oligopeptide cotransporter PepT1.
1997,
Pubmed
,
Xenbase
Ostaszewska,
The effect of plant protein-based diet supplemented with dipeptide or free amino acids on digestive tract morphology and PepT1 and PepT2 expressions in common carp (Cyprinus carpio L.).
2010,
Pubmed
Parker,
Cryo-EM structure of PepT2 reveals structural basis for proton-coupled peptide and prodrug transport in mammals.
2021,
Pubmed
Peres,
Electrophysiological insights into the mechanism of ion-coupled cotransporters.
2004,
Pubmed
Pieri,
The transmembrane tyrosines Y56, Y91 and Y167 play important roles in determining the affinity and transport rate of the rabbit proton-coupled peptide transporter PepT1.
2009,
Pubmed
,
Xenbase
Renna,
Functional and structural determinants of reverse operation in the pH-dependent oligopeptide transporter PepT1.
2011,
Pubmed
,
Xenbase
Renna,
Unified modeling of the mammalian and fish proton-dependent oligopeptide transporter PepT1.
2011,
Pubmed
,
Xenbase
Romano,
Teleost fish models in membrane transport research: the PEPT1(SLC15A1) H+-oligopeptide transporter as a case study.
2014,
Pubmed
Romano,
High-affinity peptide transporter PEPT2 (SLC15A2) of the zebrafish Danio rerio: functional properties, genomic organization, and expression analysis.
2006,
Pubmed
,
Xenbase
Rønnestad,
Molecular cloning and functional expression of atlantic salmon peptide transporter 1 in Xenopus oocytes reveals efficient intestinal uptake of lysine-containing and other bioactive di- and tripeptides in teleost fish.
2010,
Pubmed
,
Xenbase
Rubio-Aliaga,
Cloning and characterization of the gene encoding the mouse peptide transporter PEPT2.
2000,
Pubmed
,
Xenbase
Rühl,
Functional expression of the peptide transporter PEPT2 in the mammalian enteric nervous system.
2005,
Pubmed
Saito,
Molecular cloning and tissue distribution of rat peptide transporter PEPT2.
1996,
Pubmed
,
Xenbase
Sala-Rabanal,
Molecular mechanism of dipeptide and drug transport by the human renal H+/oligopeptide cotransporter hPEPT2.
2008,
Pubmed
,
Xenbase
Sangaletti,
Functional expression of the oligopeptide transporter PepT1 from the sea bass (Dicentrarchus labrax).
2009,
Pubmed
,
Xenbase
Smith,
Proton-coupled oligopeptide transporter family SLC15: physiological, pharmacological and pathological implications.
2013,
Pubmed
Terada,
Structural requirements for determining the substrate affinity of peptide transporters PEPT1 and PEPT2.
2000,
Pubmed
Torreilles,
Evaluation and refinement of euthanasia methods for Xenopus laevis.
2009,
Pubmed
,
Xenbase
Vacca,
The peptide transporter 1a of the zebrafish Danio rerio, an emerging model in nutrigenomics and nutrition research: molecular characterization, functional properties, and expression analysis.
2019,
Pubmed
,
Xenbase
Verri,
Di- and tripeptide transport in vertebrates: the contribution of teleost fish models.
2017,
Pubmed
Verri,
Molecular and functional characterisation of the zebrafish (Danio rerio) PEPT1-type peptide transporter.
2003,
Pubmed
,
Xenbase
Verri,
Peptide transport and animal growth: the fish paradigm.
2011,
Pubmed
Viennois,
Function, Regulation, and Pathophysiological Relevance of the POT Superfamily, Specifically PepT1 in Inflammatory Bowel Disease.
2018,
Pubmed
Wada,
Functional linkage of H+/peptide transporter PEPT2 and Na+/H+ exchanger in primary cultures of astrocytes from mouse cerebral cortex.
2005,
Pubmed
Wang,
Electrophysiological characteristics of the proton-coupled peptide transporter PEPT2 cloned from rat brain.
1998,
Pubmed
,
Xenbase
Waterhouse,
SWISS-MODEL: homology modelling of protein structures and complexes.
2018,
Pubmed
Xu,
Functional role of the intracellular loop linking transmembrane domains 6 and 7 of the human dipeptide transporter hPEPT1.
2010,
Pubmed
Ye,
Primer-BLAST: a tool to design target-specific primers for polymerase chain reaction.
2012,
Pubmed
Zhao,
Substrates of the human oligopeptide transporter hPEPT2.
2015,
Pubmed
