-
Annual Review of Pharmacology and... Jan 2023The coordinated movement of organic anions (e.g., drugs, metabolites, signaling molecules, nutrients, antioxidants, gut microbiome products) between tissues and body... (Review)
Review
The coordinated movement of organic anions (e.g., drugs, metabolites, signaling molecules, nutrients, antioxidants, gut microbiome products) between tissues and body fluids depends, in large part, on organic anion transporters (OATs) [solute carrier 22 (SLC22)], organic anion transporting polypeptides (OATPs) [solute carrier organic (SLCO)], and multidrug resistance proteins (MRPs) [ATP-binding cassette, subfamily C (ABCC)]. Depending on the range of substrates, transporters in these families can be considered multispecific, oligospecific, or (relatively) monospecific. Systems biology analyses of these transporters in the context of expression patterns reveal they are hubs in networks involved in interorgan and interorganismal communication. The remote sensing and signaling theory explains how the coordinated functions of drug transporters, drug-metabolizing enzymes, and regulatory proteins play a role in optimizing systemic and local levels of important endogenous small molecules. We focus on the role of OATs, OATPs, and MRPs in endogenous metabolism and how their substrates (e.g., bile acids, short chain fatty acids, urate, uremic toxins) mediate interorgan and interorganismal communication and help maintain and restore homeostasis in healthy and disease states.
Topics: Humans; Avena; Remote Sensing Technology; Membrane Transport Proteins; Organic Anion Transporters; Adenosine Triphosphate
PubMed: 36206988
DOI: 10.1146/annurev-pharmtox-030322-084058 -
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 -
International Journal of Molecular... Feb 2023The kidney functions not only as a metabolite elimination organ but also plays an important role in pharmacotherapy. The kidney tubule epithelia cells express membrane... (Review)
Review
The kidney functions not only as a metabolite elimination organ but also plays an important role in pharmacotherapy. The kidney tubule epithelia cells express membrane carriers and transporters, which play an important role in drug elimination, and can determine drug nephrotoxicity and drug-drug interactions, as well as constituting direct drug targets. The above aspects of kidney transport proteins are discussed in the review.
Topics: Humans; Membrane Transport Proteins; Kidney; Carrier Proteins; Drug-Related Side Effects and Adverse Reactions; Drug Interactions; Organic Anion Transporters
PubMed: 36769175
DOI: 10.3390/ijms24032856 -
Biomolecules Nov 2019Plastids, organelles that evolved from cyanobacteria via endosymbiosis in eukaryotes, provide carbohydrates for the formation of biomass and for mitochondrial energy... (Review)
Review
Plastids, organelles that evolved from cyanobacteria via endosymbiosis in eukaryotes, provide carbohydrates for the formation of biomass and for mitochondrial energy production to the cell. They generate their own energy in the form of the nucleotide adenosine triphosphate (ATP). However, plastids of non-photosynthetic tissues, or during the dark, depend on external supply of ATP. A dedicated antiporter that exchanges ATP against adenosine diphosphate (ADP) plus inorganic phosphate (Pi) takes over this function in most photosynthetic eukaryotes. Additional forms of such nucleotide transporters (NTTs), with deviating activities, are found in intracellular bacteria, and, surprisingly, also in diatoms, a group of algae that acquired their plastids from other eukaryotes via one (or even several) additional endosymbioses compared to algae with primary plastids and higher plants. In this review, we summarize what is known about the nucleotide synthesis and transport pathways in diatom cells, and discuss the evolutionary implications of the presence of the additional NTTs in diatoms, as well as their applications in biotechnology.
Topics: Biological Evolution; Biological Transport; Biotechnology; Diatoms; Membrane Transport Proteins; Nucleotides
PubMed: 31766535
DOI: 10.3390/biom9120761 -
Nature Communications May 2023The kidney plays a key role in the correction of systemic acid-base imbalances. Central for this regulation are the intercalated cells in the distal nephron, which...
The kidney plays a key role in the correction of systemic acid-base imbalances. Central for this regulation are the intercalated cells in the distal nephron, which secrete acid or base into the urine. How these cells sense acid-base disturbances is a long-standing question. Intercalated cells exclusively express the Na-dependent Cl/HCO exchanger AE4 (Slc4a9). Here we show that AE4-deficient mice exhibit a major dysregulation of acid-base balance. By combining molecular, imaging, biochemical and integrative approaches, we demonstrate that AE4-deficient mice are unable to sense and appropriately correct metabolic alkalosis and acidosis. Mechanistically, a lack of adaptive base secretion via the Cl/HCO exchanger pendrin (Slc26a4) is the key cellular cause of this derailment. Our findings identify AE4 as an essential part of the renal sensing mechanism for changes in acid-base status.
Topics: Mice; Animals; Kidney; Membrane Transport Proteins; Acid-Base Equilibrium; Nephrons; Sulfate Transporters; Bicarbonates; Chloride-Bicarbonate Antiporters
PubMed: 37236964
DOI: 10.1038/s41467-023-38562-x -
Microbiology (Reading, England) Feb 2021
Topics: Biofilms; Biological Transport; Haloferax volcanii; Humans; Membrane Transport Proteins; Microbiology; Mycobacterium tuberculosis; Periodicals as Topic; Pseudomonas; Ribosomes; Streptomyces; Vibrio cholerae
PubMed: 33635187
DOI: 10.1099/mic.0.001046 -
Advances in Neurobiology 2023Monoamine transporters (MATs) are targets of a wide range of compounds that have been developed as therapeutic treatments for various neuropsychiatric and... (Review)
Review
Monoamine transporters (MATs) are targets of a wide range of compounds that have been developed as therapeutic treatments for various neuropsychiatric and neurodegenerative disorders such as depression, ADHD, neuropathic pain, anxiety disorders, stimulant use disorders, epilepsy, and Parkinson's disease. The MAT family is comprised of three main members - the dopamine transporter (DAT), the norepinephrine transporter (NET), and the serotonin transporter (SERT). These transporters are through reuptake responsible for the clearance of their respective monoamine substrates from the extracellular space. The determination of X-ray crystal structures of MATs and their homologues bound with various substrates and ligands has resulted in a surge of structure-function-based studies of MATs to understand the molecular basis of transport function and the mechanism of various ligands that ultimately result in their behavioral effects. This review focusses on recent examples of ligand-based structure-activity relationship studies trying to overcome some of the challenges associated with previously developed MAT inhibitors. These studies have led to the discovery of unique and novel structurally diverse MAT ligands including allosteric modulators. These novel molecular scaffolds serve as leads for designing more effective therapeutic interventions by modulating the activities of MATs and ultimately their associated neurotransmission and behavioral effects.
Topics: Humans; Biological Transport; Ligands; Serotonin Plasma Membrane Transport Proteins; Vesicular Monoamine Transport Proteins; Mental Disorders; Drug Discovery
PubMed: 36928847
DOI: 10.1007/978-3-031-21054-9_4 -
Frontiers in Cellular and Infection... 2019
Topics: Bacteria; Bacterial Proteins; Bacterial Secretion Systems; Host-Pathogen Interactions; Membrane Transport Proteins; Protein Transport
PubMed: 32039049
DOI: 10.3389/fcimb.2019.00473 -
Disease Models & Mechanisms Nov 2023By controlling the passage of small molecules across lipid bilayers, membrane transporters influence not only the uptake and efflux of nutrients, but also the metabolic... (Review)
Review
By controlling the passage of small molecules across lipid bilayers, membrane transporters influence not only the uptake and efflux of nutrients, but also the metabolic state of the cell. With more than 450 members, the Solute Carriers (SLCs) are the largest transporter super-family, clustering into families with different substrate specificities and regulatory properties. Cells of different types are, therefore, able to tailor their transporter expression signatures depending on their metabolic requirements, and the physiological importance of these proteins is illustrated by their mis-regulation in a number of disease states. In cancer, transporter expression is heterogeneous, and the SLC family has been shown to facilitate the accumulation of biomass, influence redox homeostasis, and also mediate metabolic crosstalk with other cell types within the tumour microenvironment. This Review explores the roles of membrane transporters in physiological and malignant settings, and how these roles can affect drug response, through either indirect modulation of sensitivity or the direct transport of small-molecule therapeutic compounds into cells.
Topics: Humans; Membrane Transport Proteins; Solute Carrier Proteins; Biological Transport; Neoplasms; Cell Physiological Phenomena; Tumor Microenvironment
PubMed: 38037877
DOI: 10.1242/dmm.050404 -
Biomolecules Nov 2020Mitochondrial carriers facilitate the transfer of small molecules across the inner mitochondrial membrane (IMM) to support mitochondrial function and core cellular... (Review)
Review
Mitochondrial carriers facilitate the transfer of small molecules across the inner mitochondrial membrane (IMM) to support mitochondrial function and core cellular processes. In addition to the classical SLC25 (solute carrier family 25) mitochondrial carriers, the past decade has led to the discovery of additional protein families with numerous members that exhibit IMM localization and transporter-like properties. These include mitochondrial pyruvate carriers, sideroflexins, and mitochondrial cation/H exchangers. These transport proteins were linked to vital physiological functions and disease. Their structures and transport mechanisms are, however, still largely unknown and understudied. Protein sequence analysis per se can often pinpoint hotspots that are of functional or structural importance. In this review, we summarize current knowledge about the sequence features of mitochondrial transporters with a special focus on the newly included SLC54, SLC55 and SLC56 families of the SLC solute carrier superfamily. Taking a step further, we combine sequence conservation analysis with transmembrane segment and secondary structure prediction methods to extract residue positions and sequence motifs that likely play a role in substrate binding, binding site gating or structural stability. We hope that our review will help guide future experimental efforts by the scientific community to unravel the transport mechanisms and structures of these novel mitochondrial carriers.
Topics: Humans; Mitochondria; Mitochondrial Membrane Transport Proteins; Protein Structure, Secondary; Sequence Analysis, Protein
PubMed: 33260588
DOI: 10.3390/biom10121611