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Current Opinion in Nephrology and... Sep 2019Studies of the genetic model organism, Drosophila melanogaster, have unraveled molecular pathways relevant to human physiology and disease. The Malpighian tubule, the... (Review)
Review
PURPOSE OF REVIEW
Studies of the genetic model organism, Drosophila melanogaster, have unraveled molecular pathways relevant to human physiology and disease. The Malpighian tubule, the Drosophila renal epithelium, is described here, including tools available to study transport; conserved transporters, channels, and the signaling pathways regulating them; and fly models of kidney stone disease.
RECENT FINDINGS
Tools to measure Malpighian tubule transport continue to advance, including use of a transgenic sensor to quantify intracellular pH and proton fluxes. A recent study generated an RNA-sequencing-based atlas of tissue-specific gene expression, with resulting insights into Malpighian tubule gene expression of transporters and channels. Advances have been made in understanding the molecular physiology of the With No Lysine kinase-Ste20-related proline/alanine rich kinase/oxidative stress response kinase cascade that regulates epithelial ion transport in flies and mammals. New studies in Drosophila kidney stone models have characterized zinc transporters and used Malpighian tubules to study the efficacy of a plant metabolite in decreasing stone burden.
SUMMARY
Study of the Drosophila Malpighian tubule affords opportunities to better characterize the molecular physiology of epithelial transport mechanisms relevant to mammalian renal physiology.
Topics: Animals; Disease Models, Animal; Drosophila melanogaster; Humans; Ion Transport; Kidney Calculi; Kidney Diseases; Malpighian Tubules; Signal Transduction
PubMed: 31268918
DOI: 10.1097/MNH.0000000000000521 -
International Journal of Molecular... Dec 2022The plasma-membrane homeostasis Na/Ca exchangers (NCXs) mediate Ca extrusion/entry to dynamically shape Ca signaling/in biological systems ranging from bacteria to... (Review)
Review
The plasma-membrane homeostasis Na/Ca exchangers (NCXs) mediate Ca extrusion/entry to dynamically shape Ca signaling/in biological systems ranging from bacteria to humans. The NCX gene orthologs, isoforms, and their splice variants are expressed in a tissue-specific manner and exhibit nearly 10-fold differences in the transport rates and regulatory specificities to match the cell-specific requirements. Selective pharmacological targeting of NCX variants could benefit many clinical applications, although this intervention remains challenging, mainly because a full-size structure of eukaryotic NCX is unavailable. The crystal structure of the archaeal NCX_Mj, in conjunction with biophysical, computational, and functional analyses, provided a breakthrough in resolving the ion transport mechanisms. However, NCX_Mj (whose size is nearly three times smaller than that of mammalian NCXs) cannot serve as a structure-dynamic model for imitating high transport rates and regulatory modules possessed by eukaryotic NCXs. The crystal structures of isolated regulatory domains (obtained from eukaryotic NCXs) and their biophysical analyses by SAXS, NMR, FRET, and HDX-MS approaches revealed structure-based variances of regulatory modules. Despite these achievements, it remains unclear how multi-domain interactions can decode and integrate diverse allosteric signals, thereby yielding distinct regulatory outcomes in a given ortholog/isoform/splice variant. This article summarizes the relevant issues from the perspective of future developments.
Topics: Animals; Humans; Scattering, Small Angle; X-Ray Diffraction; Protein Isoforms; Ion Transport; Eukaryotic Cells; Sodium-Calcium Exchanger; Calcium; Mammals
PubMed: 36613523
DOI: 10.3390/ijms24010061 -
Physiology (Bethesda, Md.) Sep 2017Clinical assessment of acid-base disorders depends on measurements made in the blood, part of the extracellular compartment. Yet much of the metabolic importance of... (Review)
Review
Clinical assessment of acid-base disorders depends on measurements made in the blood, part of the extracellular compartment. Yet much of the metabolic importance of these disorders concerns intracellular events. Intracellular and interstitial compartment acid-base balance is complex and heterogeneous. This review considers the determinants of the extracellular fluid pH related to the ion transport processes at the interface of cells and the interstitial fluid, and between epithelial cells lining the transcellular contents of the gastrointestinal and urinary tracts that open to the external environment. The generation of acid-base disorders and the associated disruption of electrolyte balance are considered in the context of these membrane transporters. This review suggests a process of internal and external balance for pH regulation, similar to that of potassium. The role of secretory gastrointestinal epithelia and renal epithelia with respect to normal pH homeostasis and clinical disorders are considered. Electroneutrality of electrolytes in the ECF is discussed in the context of reciprocal changes in Cl or non Cl anions and [Formula: see text].
Topics: Acid-Base Equilibrium; Body Fluid Compartments; Homeostasis; Humans; Hydrogen-Ion Concentration; Ion Transport; Water-Electrolyte Balance
PubMed: 28814497
DOI: 10.1152/physiol.00007.2017 -
Sheng Li Xue Bao : [Acta Physiologica... Jun 2016Ion channels and transporters represent two major types of pathways of transmembrane transport for ions. Distinct from ion channels which conduct passive ionic... (Review)
Review
Ion channels and transporters represent two major types of pathways of transmembrane transport for ions. Distinct from ion channels which conduct passive ionic diffusion, ion transporters mediate active transport of ions. In the perspective of biochemistry, ion transporters are enzymes that catalyze the movement of ions across the plasma membrane. In the present review, we selected the Na(+)/HCO3(-) cotransporter (NBC) as an example to analyze the key biochemical and biophysical properties of ion transporters, including stoichiometry, turnover number and transport capacity. Moreover, we provided an analysis of the electrophysiological principles of NBC based on the laws of thermodynamics. Based on the thermodynamical analysis, we showed how the stoichiometry of an NBC determines the direction of its ion transport. Finally, we reviewed the methodology for experimental determination of the stoichiometry of NBC, as well as the physiological significance of the stoichiometry of NBCs in specific tissues.
Topics: Electrophysiological Phenomena; Ion Transport; Sodium-Bicarbonate Symporters
PubMed: 27350205
DOI: No ID Found -
Advances in Experimental Medicine and... 2021Ion-transporting microbial rhodopsins are widely used as major molecular tools in optogenetics. They are categorized into light-gated ion channels and light-driven ion... (Review)
Review
Ion-transporting microbial rhodopsins are widely used as major molecular tools in optogenetics. They are categorized into light-gated ion channels and light-driven ion pumps. While the former passively transport various types of cations and anions in a light-dependent manner, light-driven ion pumps actively transport specific ions, such as H, Na, Cl, against electrophysiological potential by using light energy. Since the ion transport by these pumps induces hyperpolarization of membrane potential and inhibit neural firing, light-driven ion-pumping rhodopsins are mostly applied as inhibitory optogenetics tools. Recent progress in genome and metagenome sequencing identified more than several thousands of ion-pumping rhodopsins from a wide variety of microbes, and functional characterization studies has been revealing many new types of light-driven ion pumps one after another. Since light-gated channels were reviewed in other chapters in this book, here the rapid progress in functional characterization, molecular mechanism study, and optogenetic application of ion-pumping rhodopsins were reviewed.
Topics: Ion Pumps; Ion Transport; Light; Optogenetics; Rhodopsins, Microbial
PubMed: 33398809
DOI: 10.1007/978-981-15-8763-4_6 -
Journal of Biosciences Sep 2016Copper, although known as a micronutrient, has a pivotal role in modulating the cellular metabolism. Many studies have reported the role of copper in angiogenesis.... (Review)
Review
Copper, although known as a micronutrient, has a pivotal role in modulating the cellular metabolism. Many studies have reported the role of copper in angiogenesis. Copper chaperones are intracellular proteins that mediate copper trafficking to various cell organelles. However, the role and function of copper chaperones in relation to angiogenesis has to be further explored. The intracellular copper levels when in excess are deleterious and certain mutations of copper chaperones have been shown to induce cell death and influence various cellular metabolisms. The study of these chaperones will be helpful in understanding the players in the cascade of events in angiogenesis and their role in cellular metabolic pathways. In this review we have briefly listed the copper chaperones associated with angiogenic and metabolic signalling and their function.
Topics: Copper; Humans; Ion Transport; Metabolic Networks and Pathways; Molecular Chaperones; Neovascularization, Physiologic
PubMed: 27581939
DOI: 10.1007/s12038-016-9629-6 -
American Journal of Physiology. Cell... Dec 2021The major transmembrane protein of the red blood cell, known as band 3, AE1, and SLC4A1, has two main functions: ) catalysis of Cl/[Formula: see text] exchange, one of... (Review)
Review
The major transmembrane protein of the red blood cell, known as band 3, AE1, and SLC4A1, has two main functions: ) catalysis of Cl/[Formula: see text] exchange, one of the steps in CO excretion, and ) anchoring the membrane skeleton. This review summarizes the 150-year history of research on red cell anion transport and band 3 as an experimental system for studying membrane protein structure and ion transport mechanisms. Important early findings were that red cell Cl transport is a tightly coupled 1:1 exchange and band 3 is labeled by stilbenesulfonate derivatives that inhibit anion transport. Biochemical studies showed that the protein is dimeric or tetrameric (paired dimers) and that there is one stilbenedisulfonate binding site per subunit of the dimer. Transport kinetics and inhibitor characteristics supported the idea that the transporter acts by an alternating access mechanism with intrinsic asymmetry. The sequence of band 3 cDNA provided a framework for detailed study of protein topology and amino acid residues important for transport. The identification of genetic variants produced insights into the roles of band 3 in red cell abnormalities and distal renal tubular acidosis. The publication of the membrane domain crystal structure made it possible to propose concrete molecular models of transport. Future research directions include improving our understanding of the transport mechanism at the molecular level and of the integrative relationships among band 3, hemoglobin, carbonic anhydrase, and gradients (both transmembrane and subcellular) of [Formula: see text], Cl, O, CO, pH, and nitric oxide (NO) metabolites during pulmonary and systemic capillary gas exchange.
Topics: Animals; Anion Exchange Protein 1, Erythrocyte; Cell Membrane; Cell Physiological Phenomena; Erythrocytes; Humans; Ion Transport; Membrane Transport Proteins
PubMed: 34669510
DOI: 10.1152/ajpcell.00275.2021 -
ChemPlusChem Nov 2022The development of synthetic anion transporters is motivated by their potential application as treatment for diseases that originate from deficient anion transport by... (Review)
Review
The development of synthetic anion transporters is motivated by their potential application as treatment for diseases that originate from deficient anion transport by natural proteins. Transport of bicarbonate is important for crucial biological functions such as respiration and digestion. Despite this biological relevance, bicarbonate transport has not been as widely studied as chloride transport. Herein we present an overview of the synthetic receptors that have been studied as bicarbonate transporters, together with the different assays used to perform transport studies in large unilamellar vesicles. We highlight the most active transporters and comment on the nature of the functional groups present in active and inactive compounds. We also address recent mechanistic studies that have revealed different processes that can lead to net transport of bicarbonate, as well as studies reported in cells and tissues, and comment on the key challenges for the further development of bicarbonate transporters.
Topics: Bicarbonates; Biological Transport; Ion Transport
PubMed: 36414387
DOI: 10.1002/cplu.202200266 -
International Journal of Molecular... Jan 2024This Special Issue focuses on the significance of ion-transporting proteins, such as ion channels and transporters, providing evidence for their significant contribution...
This Special Issue focuses on the significance of ion-transporting proteins, such as ion channels and transporters, providing evidence for their significant contribution to bodily and cellular functions via the regulation of signal transduction and ionic environments [...].
Topics: Humans; Ion Channels; Ion Transport; Signal Transduction
PubMed: 38339004
DOI: 10.3390/ijms25031726 -
Current Opinion in Plant Biology Dec 2014The biochemical characterization of cation/H(+) exchange has been known since 1985 [1], yet only recently have we begun to understand the contribution of individual... (Review)
Review
The biochemical characterization of cation/H(+) exchange has been known since 1985 [1], yet only recently have we begun to understand the contribution of individual exchangers to ion homeostasis in plants. One particularly important class of exchangers is the NHX-type that is associated with Na(+) transport and therefore salinity tolerance. New evidence suggests that under normal growth conditions NHXs are critical regulators of K(+) and pH homeostasis and have important roles, depending on their cellular localization, in the generation of turgor as well as in vesicular trafficking. Recent advances highlight novel and exciting functions of intracellular NHXs in growth and development, stress adaptation and osmotic adjustment. Here, we elaborate on new and emerging cellular and physiological functions of this group of H(+)-coupled cation exchangers.
Topics: Gene Expression Regulation, Plant; Homeostasis; Ion Transport; Plant Proteins; Potassium
PubMed: 25173972
DOI: 10.1016/j.pbi.2014.08.002