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International Journal of Molecular... Aug 2022Na/H exchangers are essential for Na and pH homeostasis in all organisms. Human Na/H exchangers are of high medical interest, and insights into their structure and... (Review)
Review
Na/H exchangers are essential for Na and pH homeostasis in all organisms. Human Na/H exchangers are of high medical interest, and insights into their structure and function are aided by the investigation of prokaryotic homologues. Most prokaryotic Na/H exchangers belong to either the Cation/Proton Antiporter (CPA) superfamily, the Ion Transport (IT) superfamily, or the Na-translocating Mrp transporter superfamily. Several structures have been solved so far for CPA and Mrp members, but none for the IT members. NhaA from has served as the prototype of Na/H exchangers due to the high amount of structural and functional data available. Recent structures from other CPA exchangers, together with diverse functional information, have allowed elucidation of some common working principles shared by Na/H exchangers from different families, such as the type of residues involved in the substrate binding and even a simple mechanism sufficient to explain the pH regulation in the CPA and IT superfamilies. Here, we review several aspects of prokaryotic Na/H exchanger structure and function, discussing the similarities and differences between different transporters, with a focus on the CPA and IT exchangers. We also discuss the proposed transport mechanisms for Na/H exchangers that explain their highly pH-regulated activity profile.
Topics: Escherichia coli; Escherichia coli Proteins; Humans; Hydrogen-Ion Concentration; Ion Transport; Sodium; Sodium-Hydrogen Exchangers
PubMed: 36012428
DOI: 10.3390/ijms23169156 -
Archives of Biochemistry and Biophysics Dec 2014Skin melanocytes and ocular pigment cells contain specialized organelles called melanosomes, which are responsible for the synthesis of melanin, the major pigment in... (Review)
Review
Skin melanocytes and ocular pigment cells contain specialized organelles called melanosomes, which are responsible for the synthesis of melanin, the major pigment in mammals. Defects in the complex mechanisms involved in melanin synthesis and regulation result in vision and pigmentation deficits, impaired development of the visual system, and increased susceptibility to skin and eye cancers. Ion transport across cellular membranes is critical for many biological processes, including pigmentation, but the molecular mechanisms by which it regulates melanin synthesis, storage, and transfer are not understood. In this review we first discuss ion channels and transporters that function at the plasma membrane of melanocytes; in the second part we consider ion transport across the membrane of intracellular organelles, with emphasis on melanosomes. We discuss recently characterized lysosomal and endosomal ion channels and transporters associated with pigmentation phenotypes. We then review the evidence for melanosomal channels and transporters critical for pigmentation, discussing potential molecular mechanisms mediating their function. The studies investigating ion transport in pigmentation physiology open new avenues for future research and could reveal novel molecular mechanisms underlying melanogenesis.
Topics: Animals; Calcium Signaling; Endosomes; Humans; Intracellular Membranes; Ion Channels; Ion Transport; Lysosomes; Melanins; Melanocytes; Melanosomes; Membrane Potentials; Pigmentation
PubMed: 25034214
DOI: 10.1016/j.abb.2014.06.020 -
American Journal of Physiology. Cell... Jan 2019Mucociliary clearance is critically important in protecting the airways from infection and from the harmful effects of smoke and various inspired substances known to... (Review)
Review
Mucociliary clearance is critically important in protecting the airways from infection and from the harmful effects of smoke and various inspired substances known to induce oxidative stress and persistent inflammation. An essential feature of the clearance mechanism involves regulation of the periciliary liquid layer on the surface of the airway epithelium, which is necessary for normal ciliary beating and maintenance of mucus hydration. The underlying ion transport processes associated with airway surface hydration include epithelial Na channel-dependent Na absorption occurring in parallel with CFTR and Ca-activated Cl channel-dependent anion secretion, which are coordinately regulated to control the depth of the periciliary liquid layer. Oxidative stress is known to cause both acute and chronic effects on airway ion transport function, and an increasing number of studies in the past few years have identified an important role for autophagy as part of the physiological response to the damaging effects of oxidation. In this review, recent studies addressing the influence of oxidative stress and autophagy on airway ion transport pathways, along with results showing the potential of autophagy modulators in restoring the function of ion channels involved in transepithelial electrolyte transport necessary for effective mucociliary clearance, are presented.
Topics: Adaptor Proteins, Signal Transducing; Animals; Autophagy; Humans; Ion Transport; Mucociliary Clearance; Oxidative Stress; Respiratory Mechanics
PubMed: 30303690
DOI: 10.1152/ajpcell.00341.2018 -
Magnesium Research 2015Patients with hypomagnesemia suffer from a wide range of symptoms including muscle cramps, cardiac arrhythmias and epilepsy. Disturbances in body Mg(2+) homeostasis can... (Review)
Review
Patients with hypomagnesemia suffer from a wide range of symptoms including muscle cramps, cardiac arrhythmias and epilepsy. Disturbances in body Mg(2+) homeostasis can often be attributed to increased Mg(2+) excretion by the kidney. Within the kidney, the distal convoluted tubule (DCT) segment determines the final Mg(2+) excretion, since no reabsorption takes place beyond this segment of the nephron. On 21(st) of January 2015, Jeroen de Baaij defended his thesis "The Distal Convoluted Tubule: the Art of Magnesium Transport", in which he aimed to identify new genes involved in Mg(2+) reabsorption in the DCT. This review summarizes the main findings of his graduate research. TRPM6 mediates apical Mg(2+) entry into the DCT cell and is highly regulated by EGF, insulin and pH. ATP and flavagline compounds have been characterized as new regulators of TRPM6 activity, providing novel pathways to target Mg(2+) disturbances. Using isolated primary DCT cells from mice, PCBD1 was identified as a new transcriptional regulator of Mg(2+) transport in the DCT. Indeed, patients with PCBD1 mutations were shown to suffer hypomagnesemia and MODY5-like diabetes. Subsequently, the work presented in the thesis focused on the elucidation of the basolateral Mg(2+) extrusion of the DCT cell. In vivo studies using SLC41A3-knockout mice suggest that SLC41A3 may act as Mg(2+) extrusion mechanism. CNNM2 has long been hypothesized to transport Mg(2+) at the basolateral membrane of the DCT. However, by determining the protein topology and homology modeling of the CBS domains, it was argued that CNNM2 is rather an Mg(2+)-sensing mechanism. Follow-up studies using (25)Mg(2+) isotopes showed that CNNM2 increases Mg(2+) uptake when overexpressed in HEK293 cells. Additionally, by knocking down cnnm2 in zebrafish, CNNM2 was demonstrated to be essential for brain development and Mg(2+) homeostasis. Mutations in CNNM2 were shown to cause hypomagnesemia, seizures and intellectual disability. Altogether, this thesis established the importance of Mg(2+) reabsorption in the DCT to health and disease. Combined, continued efforts of clinicians, geneticists, and researchers are necessary to improve the care of hypomagnesemic patients and increase our understanding of Mg(2+) reabsorption in the DCT.
Topics: Animals; Homeostasis; Humans; Ion Transport; Magnesium; Signal Transduction; TRPM Cation Channels
PubMed: 26446763
DOI: 10.1684/mrh.2015.0388 -
Trends in Plant Science Feb 2017Grasses began to diversify in the late Cretaceous Period and now dominate more than one third of global land area, including three-quarters of agricultural land. We... (Review)
Review
Grasses began to diversify in the late Cretaceous Period and now dominate more than one third of global land area, including three-quarters of agricultural land. We hypothesize that their success is likely attributed to the evolution of highly responsive stomata capable of maximizing productivity in rapidly changing environments. Grass stomata harness the active turgor control mechanisms present in stomata of more ancient plant lineages, maximizing several morphological and developmental features to ensure rapid responses to environmental inputs. The evolutionary development of grass stomata appears to have been a gradual progression. Therefore, understanding the complex structures, developmental events, regulatory networks, and combinations of ion transporters necessary to drive rapid stomatal movement may inform future efforts towards breeding new crop varieties.
Topics: Biological Evolution; Evolution, Molecular; Ion Transport; Plant Proteins; Plant Stomata; Poaceae
PubMed: 27776931
DOI: 10.1016/j.tplants.2016.09.005 -
Angewandte Chemie (International Ed. in... Jun 2023The design of ion-selective membranes is the key towards efficient reverse electrodialysis-based osmotic power conversion. The tradeoff between ion selectivity (output... (Review)
Review
The design of ion-selective membranes is the key towards efficient reverse electrodialysis-based osmotic power conversion. The tradeoff between ion selectivity (output voltage) and ion permeability (output current) in existing porous membranes, however, limits the upgradation of power generation efficiency for practical applications. Thus, we provide the simple guidelines based on fundamentals of ion transport in nanofluidics for promoting osmotic power conversion. In addition, we discuss strategies for optimizing membrane performance through analysis of various material parameters in membrane design, such as pore size, surface charge, pore density, membrane thickness, ion pathway, pore order, and ionic diode effect. Lastly, a perspective on the future directions of membrane design to further maximize the efficiency of osmotic power conversion is outlined.
Topics: Permeability; Ion Transport; Porosity
PubMed: 37010943
DOI: 10.1002/anie.202303582 -
Current Opinion in Pharmacology Dec 2018
Topics: Cystic Fibrosis; Epithelial Sodium Channels; Humans; Ion Transport
PubMed: 30502021
DOI: 10.1016/j.coph.2018.11.003 -
Analytical Chemistry Apr 2022Single-molecule detection and characterization with nanopores is a powerful technique that does not require labeling. Multinanopore systems, especially double nanopores,...
Single-molecule detection and characterization with nanopores is a powerful technique that does not require labeling. Multinanopore systems, especially double nanopores, have attracted wide attention and have been applied in many fields. However, theoretical studies of electrokinetic ion transport in nanopores mainly focus on single nanopores. In this paper, for the first time, a theoretical study of pH-regulated double-barreled nanopores is conducted using three-dimensional Poisson-Nernst-Planck equations and Navier-Stokes equations. Four ionic species and the surface chemistry on the walls of the nanopores are included. The results demonstrate that the properties of the bulk salt solution significantly affect nanopore conductivity and ion transport phenomena in nanopores. There are two ion-enriched zones and two ion-depleted zones in double-barreled nanopores. Due to the symmetry of the double-barreled nanopore structure and surface charge density, there is no ionic rectification effect in double-barreled nanopores. The ion selectivity is similar to that of conventional single pH-regulated nanopores.
Topics: Hydrogen-Ion Concentration; Ion Transport; Ions; Nanopores; Nanotechnology
PubMed: 35352923
DOI: 10.1021/acs.analchem.1c05654 -
Journal of Dental Research Mar 2017Hypomineralization of developing enamel is associated with changes in ameloblast modulation during the maturation stage. Modulation (or pH cycling) involves the cyclic... (Review)
Review
Hypomineralization of developing enamel is associated with changes in ameloblast modulation during the maturation stage. Modulation (or pH cycling) involves the cyclic transformation of ruffle-ended (RE) ameloblasts facing slightly acidic enamel into smooth-ended (SE) ameloblasts near pH-neutral enamel. The mechanism of ameloblast modulation is not clear. Failure of ameloblasts of Cftr-null and anion exchanger 2 ( Ae2)-null mice to transport Cl into enamel acidifies enamel, prevents modulation, and reduces mineralization. It suggests that pH regulation is critical for modulation and for completion of enamel mineralization. This report presents a review of the major types of transmembrane molecules that ameloblasts express to transport calcium to form crystals and bicarbonates to regulate pH. The type of transporter depends on the developmental stage. Modulation is proposed to be driven by the pH of enamel fluid and the compositional and/or physicochemical changes that result from increased acidity, which may turn RE ameloblasts into SE mode. Amelogenins delay outgrowth of crystals and keep the intercrystalline space open for diffusion of mineral ions into complete depth of enamel. Modulation enables stepwise removal of amelogenins from the crystal surface, their degradation, and removal from the enamel. Removal of matrix allows slow expansion of crystals. Modulation also reduces the stress that ameloblasts experience when exposed to high acid levels generated by mineral formation or by increased intracellular Ca. By cyclically interrupting Ca transport by RE ameloblasts and their transformation into SE ameloblasts, proton production ceases shortly and enables the ameloblasts to recover. Modulation also improves enamel crystal quality by selectively dissolving immature Ca-poor crystals, removing impurities as Mg and carbonates, and recrystallizing into more acid-resistant crystals.
Topics: Ameloblasts; Amelogenesis; Animals; Chloride-Bicarbonate Antiporters; Cystic Fibrosis Transmembrane Conductance Regulator; Dental Enamel; Hydrogen-Ion Concentration; Ion Transport; Mice
PubMed: 28221098
DOI: 10.1177/0022034516681768 -
ACS Nano Aug 2021Enantioselective sensing and separation are major challenges. Nanochannel technologies are energy-saving and efficient for membrane separation. Herein, inspired by...
Enantioselective sensing and separation are major challenges. Nanochannel technologies are energy-saving and efficient for membrane separation. Herein, inspired by biological antiporter proteins, artificial nanochannels with antiporter behavior were fabricated for chiral sensing and separation. Tyrosine enantiomers were incorporated into hourglass-shaped nanochannels via stepwise modifications to fabricating multiligand-modified asymmetric channels. Chiral distinction of naproxen enantiomers was amplified in the l-Tyr/d-Tyr channels, with an enantioselectivity coefficient of 524, which was over 100-fold that of one-ligand-modified nanochannels. Furthermore, transport experiments evidenced the spontaneous antiport of naproxen enantiomers in the l-Tyr/d-Tyr channels. The racemic naproxen sample was separated via the chiral antiport process, with an enantiomeric excess of 71.2%. Further analysis using electro-osmotic flow experiments and finite-element simulations confirmed that the asymmetric modified multiligand was key to achieving separation of the naproxen enantiomers. We expect these multiligand-modified asymmetric nanochannels to provide insight into mimicking biological antiporter systems and offer an approach to energy-efficient and robust enantiomer separation.
Topics: Naproxen; Stereoisomerism; Ion Transport; Antiporters
PubMed: 34319088
DOI: 10.1021/acsnano.1c02630