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International Journal of Molecular... Feb 2020This editorial aims to summarize the 19 scientific papers that contributed to this Special Issue.
This editorial aims to summarize the 19 scientific papers that contributed to this Special Issue.
Topics: Adaptor Proteins, Signal Transducing; Amino Acids; Biological Transport; Cationic Amino Acid Transporter 1; Glutamate Plasma Membrane Transport Proteins; Humans; Large Neutral Amino Acid-Transporter 1; Proteins
PubMed: 32059365
DOI: 10.3390/ijms21041212 -
Trends in Plant Science Jun 2013Abscisic acid (ABA) metabolism, perception, and transport form a triptych allowing higher plants to use ABA as a signaling molecule. The molecular bases of ABA... (Review)
Review
Abscisic acid (ABA) metabolism, perception, and transport form a triptych allowing higher plants to use ABA as a signaling molecule. The molecular bases of ABA metabolism are now well described and, over the past few years, several ABA receptors have been discovered. Although ABA transport has long been demonstrated in planta, the first breakthroughs in identifying plasma membrane-localized ABA transporters came in 2010, with the identification of two ATP-binding cassette (ABC) proteins. More recently, two ABA transporters in the nitrate transporter 1/peptide transporter (NRT1/PTR) family have been identified. In this review, we discuss the role of these different ABA transporters and examine the scientific impact of their identification. Given that the NRT1/PTR family is involved in the transport of nitrogen (N) compounds, further work should determine whether an interaction between ABA and N signaling or nutrition occurs.
Topics: ATP-Binding Cassette Transporters; Abscisic Acid; Anion Transport Proteins; Arabidopsis; Arabidopsis Proteins; Biological Transport, Active; Membrane Transport Proteins; Nitrate Transporters; Signal Transduction
PubMed: 23453706
DOI: 10.1016/j.tplants.2013.01.007 -
Methods in Enzymology 1986
Topics: Biological Transport; Escherichia coli; Membrane Transport Proteins; Mutation; Peptides; Radioisotope Dilution Technique; Salmonella typhimurium
PubMed: 3520226
DOI: 10.1016/s0076-6879(86)25031-4 -
Molecular BioSystems Jan 2008Alzheimer's disease (AD) is the most common neurodegenerative disease characterized clinically by progressive memory loss and decline in cognitive abilities and... (Review)
Review
Alzheimer's disease (AD) is the most common neurodegenerative disease characterized clinically by progressive memory loss and decline in cognitive abilities and characterized pathologically by the presence of two types of abnormal deposits, i.e., senile plaques (SP) and neurofibrillary tangles (NFT), and by extensive synapse and neuronal loss. SP are composed of fibrillar amyloid beta-peptide (Abeta) surrounded by dystrophic neurites. Recent studies suggest two prospective mechanisms for Abeta-associated membrane dysfunction and subsequent neurotoxicity. One suggests that Abeta oligomers can form heterogeneous ion-channels in the cell membrane leading to cellular degeneration, while the second suggests insertion of Abeta oligomers in membrane lipid bilayers could induce the dysfunction of ion-channels or pumps by binding to or inducing oxidative modification of membrane proteins. In this review, we discuss the effects of Abeta on membrane proteins that are involved in cholinergic and glutamatergic pathways, and some ion-channels.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Calcium Channels; Excitatory Amino Acid Transporter 2; Glutamine; Humans; Ion Transport; Membrane Transport Proteins; Models, Biological; Potassium Channels; Receptors, Cholinergic; Sodium-Potassium-Exchanging ATPase
PubMed: 18075672
DOI: 10.1039/b715278g -
Journal of Pharmaceutical Sciences Oct 2019PHT2, a member of the proton-coupled oligopeptide transporter family, participates in the transportation of small peptides and histidine from lysosomes to the cytosol....
PHT2, a member of the proton-coupled oligopeptide transporter family, participates in the transportation of small peptides and histidine from lysosomes to the cytosol. It facilitates maintenance of intracellular peptide homeostasis. However, it remains a challenge to elucidate the functional properties of PHT2 due to its localization in the lysosomal membrane. The aim of this study was to explore the transport function and substrate properties of human PHT2 (hPHT2) by transfecting Madin-Darby canine kidney cells with hPHT2 mutants to obtain stably expressed protein in the cell membrane. Using this cell model, we found that the transport activity of hPHT2 reached a maximum capacity when the extracellular pH was 5.5. hPHT2 showed relatively low affinity for Gly-Sar and relatively high affinity for d-L-histidine, with K values of 428 ± 88 μM and 66.9 ± 5.7 μM, respectively. Several typical substrates or inhibitors of PEPT1 and PEPT2, including valacyclovir, Gly-Gly-Gly, and cefadroxil but not 5-aminolevulinic acid or captopril, were proven to be substrates of hPHT2. However, hPHT2 showed low affinity for valacyclovir with a K value of 5350 ± 1234 μM. In conclusion, this study established a suitable and efficient cell model to explore the function of hPHT2 in vitro and provided important information on the transport activity and substrate properties of hPHT2.
Topics: Animals; Biological Transport; Cell Line; Cell Membrane; Dipeptides; Dogs; Histidine; Humans; Hydrogen-Ion Concentration; Lysosomes; Madin Darby Canine Kidney Cells; Membrane Transport Proteins; Oligopeptides; Peptides; Protons; Substrate Specificity
PubMed: 31254495
DOI: 10.1016/j.xphs.2019.06.016 -
Biochemical Society Transactions Oct 2011One of the principal aims of modern drug design is the targeted delivery of drugs within the body, such as to the central nervous system, combined with their exclusion... (Review)
Review
One of the principal aims of modern drug design is the targeted delivery of drugs within the body, such as to the central nervous system, combined with their exclusion from the liver and kidneys, which break down foreign molecules and subsequently eliminate them. Many of the commonly prescribed drugs are transported into cells and across the plasma membrane via endogenous membrane transporters, whose principal roles are the uptake of essential nutrients for metabolism. In many cases, such drug transport is serendipitous as they are simply mistaken as 'natural' compounds. Many of these transporters could, however, be targeted more efficiently, improving drug absorption, distribution and retention. The molecular details of these drug-transporter interactions, however, are at best poorly understood, in large part through the absence of any high-resolution structural information. To address this issue, we recently determined the structure of a prokaryotic peptide transporter, PepTSo from Shewanella oneidensis, which shares a high degree of sequence similarity and functional characteristics with the human PepT1 and PepT2 proteins. PepT1 and PepT2 contribute significantly to the oral bioavailability and pharmacokinetic properties of a number of important drug families, including antibiotics, antivirals and anticancer agents. The crystal structure of PepTSo provides the first high-resolution model of a drug importer and provides the starting point for understanding drug and peptide transport within the human body.
Topics: Anti-Bacterial Agents; Bacterial Proteins; Biological Transport; Humans; Models, Molecular; Molecular Structure; Peptide Transporter 1; Peptides; Pharmaceutical Preparations; Protein Conformation; Protons; Symporters
PubMed: 21936814
DOI: 10.1042/BST0391353 -
Journal of Controlled Release :... Nov 1999Non-invasive delivery of peptide and protein drugs will soon become a reality. This is due partly to a better understanding of the endogenous transport mechanisms,... (Review)
Review
Non-invasive delivery of peptide and protein drugs will soon become a reality. This is due partly to a better understanding of the endogenous transport mechanisms, including paracellular transport, endocytosis, and carrier-mediated transport of mucosal routes of peptide and protein drug administration. This paper focuses on work related to the elucidation of structure-function, intracellular trafficking, and regulation of the intestinal dipeptide transporter, PepT1.
Topics: Biological Transport; Biopharmaceutics; Carrier Proteins; Dipeptides; Mucous Membrane; Oligopeptides; Peptide Transporter 1; Proteins; Structure-Activity Relationship; Symporters
PubMed: 10518644
DOI: 10.1016/s0168-3659(99)00030-9 -
Nestle Nutrition Workshop Series.... 2000
Review
Topics: Adaptation, Biological; Amino Acid Transport Systems; Amino Acids; Animals; Biological Transport; Cell Membrane; Humans; Kinetics; Membrane Transport Proteins; Nutritional Support; Peptides
PubMed: 11490614
DOI: 10.1159/000061797 -
Pharmaceutical Research Nov 2023This mini-review describes the role of the solute carrier (SLC)15 family of proton-coupled oligopeptide transporters (POTs) and particularly Pept2 (Slc15A2) and PhT1... (Review)
Review
This mini-review describes the role of the solute carrier (SLC)15 family of proton-coupled oligopeptide transporters (POTs) and particularly Pept2 (Slc15A2) and PhT1 (Slc15A4) in the brain. That family transports endogenous di- and tripeptides and peptidomimetics but also a number of drugs. The review focuses on the pioneering work of David E. Smith in the field in identifying the impact of PepT2 at the choroid plexus (the blood-CSF barrier) as well as PepT2 and PhT1 in brain parenchymal cells. It also discusses recent findings and future directions in relation to brain POTs including cellular and subcellular localization, regulatory pathways, transporter structure, species differences and disease states.
Topics: Symporters; Protons; Biological Transport; Membrane Transport Proteins; Oligopeptides; Brain
PubMed: 37308743
DOI: 10.1007/s11095-023-03550-9 -
ELife Dec 2014Peptide transport plays an important role in cellular homeostasis as a key route for nitrogen acquisition in mammalian cells. PepT1 and PepT2, the mammalian proton...
Peptide transport plays an important role in cellular homeostasis as a key route for nitrogen acquisition in mammalian cells. PepT1 and PepT2, the mammalian proton coupled peptide transporters (POTs), function to assimilate and retain diet-derived peptides and play important roles in drug pharmacokinetics. A key characteristic of the POT family is the mechanism of peptide selectivity, with members able to recognise and transport >8000 different peptides. In this study, we present thermodynamic evidence that in the bacterial POT family transporter PepTSt, from Streptococcus thermophilus, at least two alternative transport mechanisms operate to move peptides into the cell. Whilst tri-peptides are transported with a proton:peptide stoichiometry of 3:1, di-peptides are co-transported with either 4 or 5 protons. This is the first thermodynamic study of proton:peptide stoichiometry in the POT family and reveals that secondary active transporters can evolve different coupling mechanisms to accommodate and transport chemically and physically diverse ligands across the membrane.
Topics: Bacterial Proteins; Membrane Transport Proteins; Protein Transport; Streptococcus thermophilus; Thermodynamics
PubMed: 25457052
DOI: 10.7554/eLife.04273