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Journal of the American Society of... May 2018
Topics: Animals; Biological Transport; Chlorides; Ion Transport; Malpighian Tubules; Signal Transduction
PubMed: 29650535
DOI: 10.1681/ASN.2018030318 -
Neuron Sep 2015Mechanotransduction, the conversion of physical forces into biochemical signals, is essential for various physiological processes such as the conscious sensations of... (Review)
Review
Mechanotransduction, the conversion of physical forces into biochemical signals, is essential for various physiological processes such as the conscious sensations of touch and hearing, and the unconscious sensation of blood flow. Mechanically activated (MA) ion channels have been proposed as sensors of physical force, but the identity of these channels and an understanding of how mechanical force is transduced has remained elusive. A number of recent studies on previously known ion channels along with the identification of novel MA ion channels have greatly transformed our understanding of touch and hearing in both vertebrates and invertebrates. Here, we present an updated review of eukaryotic ion channel families that have been implicated in mechanotransduction processes and evaluate the qualifications of the candidate genes according to specified criteria. We then discuss the proposed gating models for MA ion channels and highlight recent structural studies of mechanosensitive potassium channels.
Topics: Animals; Humans; Ion Channel Gating; Ion Channels; Ion Transport; Mechanotransduction, Cellular; Sensation; Touch
PubMed: 26402601
DOI: 10.1016/j.neuron.2015.08.032 -
Journal of Cystic Fibrosis : Official... Mar 2020Mutations associated with cystic fibrosis (CF) have complex effects on the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common CF... (Review)
Review
Mutations associated with cystic fibrosis (CF) have complex effects on the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common CF mutation, F508del, disrupts the processing to and stability at the plasma membrane and function as a Cl channel. CFTR is surrounded by a dynamic network of interacting components, referred to as the CFTR Functional Landscape, that impact its synthesis, folding, stability, trafficking and function. CFTR interacting proteins can be manipulated by functional genomic approaches to rescue the trafficking and functional defects characteristic of CF. Here we review recent efforts to elucidate the impact of genetic variation on the ability of the nascent CFTR polypeptide to interact with the proteostatic environment. We also provide an overview of how specific components of this protein network can be modulated to rescue the trafficking and functional defects associated with the F508del variant of CFTR. The identification of novel proteins playing key roles in the processing of CFTR could pave the way for their use as novel therapeutic targets to provide synergistic correction of mutant CFTR for the greater benefit of individuals with CF.
Topics: Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Genetic Therapy; Humans; Ion Transport; Membrane Transport Modulators; Mutation; Proteostasis
PubMed: 31680043
DOI: 10.1016/j.jcf.2019.10.017 -
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 -
The New Phytologist Apr 2018Content Summary 414 I. Introduction 415 II. Ca importer and exporter in plants 415 III. The Ca decoding toolkit in plants 415 IV. Mechanisms of Ca signal decoding 417 V.... (Review)
Review
Content Summary 414 I. Introduction 415 II. Ca importer and exporter in plants 415 III. The Ca decoding toolkit in plants 415 IV. Mechanisms of Ca signal decoding 417 V. Immediate Ca signaling in the regulation of ion transport 418 VI. Ca signal integration into long-term ABA responses 419 VII Integration of Ca and hormone signaling through dynamic complex modulation of the CCaMK/CYCLOPS complex 420 VIII Ca signaling in mitochondria and chloroplasts 422 IX A view beyond recent advances in Ca imaging 423 X Modeling approaches in Ca signaling 424 XI Conclusions: Ca signaling a still young blooming field of plant research 424 Acknowledgements 425 ORCID 425 References 425 SUMMARY: Temporally and spatially defined changes in Ca concentration in distinct compartments of cells represent a universal information code in plants. Recently, it has become evident that Ca signals not only govern intracellular regulation but also appear to contribute to long distance or even organismic signal propagation and physiological response regulation. Ca signals are shaped by an intimate interplay of channels and transporters, and during past years important contributing individual components have been identified and characterized. Ca signals are translated by an elaborate toolkit of Ca -binding proteins, many of which function as Ca sensors, into defined downstream responses. Intriguing progress has been achieved in identifying specific modules that interconnect Ca decoding proteins and protein kinases with downstream target effectors, and in characterizing molecular details of these processes. In this review, we reflect on recent major advances in our understanding of Ca signaling and cover emerging concepts and existing open questions that should be informative also for scientists that are currently entering this field of ever-increasing breath and impact.
Topics: Calcium; Calcium Signaling; Ion Transport; Membrane Transport Proteins; Plant Growth Regulators; Plants
PubMed: 29332310
DOI: 10.1111/nph.14966 -
Biochemical Society Transactions Dec 2021The store-operated calcium (Ca2+) entry (SOCE) is the Ca2+ entry mechanism used by cells to replenish depleted Ca2+ store. The dysregulation of SOCE has been reported in... (Review)
Review
The store-operated calcium (Ca2+) entry (SOCE) is the Ca2+ entry mechanism used by cells to replenish depleted Ca2+ store. The dysregulation of SOCE has been reported in metastatic cancer. It is believed that SOCE promotes migration and invasion by remodeling the actin cytoskeleton and cell adhesion dynamics. There is recent evidence supporting that SOCE is critical for the spatial and the temporal coding of Ca2+ signals in the cell. In this review, we critically examined the spatiotemporal control of SOCE signaling and its implication in the specificity and robustness of signaling events downstream of SOCE, with a focus on the spatiotemporal SOCE signaling during cancer cell migration, invasion and metastasis. We further discuss the limitation of our current understanding of SOCE in cancer metastasis and potential approaches to overcome such limitation.
Topics: Calcium; Calcium Signaling; Humans; Ion Transport; Neoplasm Metastasis; Neoplasms
PubMed: 34854917
DOI: 10.1042/BST20210307 -
Glia Mar 2020Glial ion transporters are important in regulation of ionic homeostasis, cell volume, and cellular signal transduction under physiological conditions of the central... (Review)
Review
Glial ion transporters are important in regulation of ionic homeostasis, cell volume, and cellular signal transduction under physiological conditions of the central nervous system (CNS). In response to acute or chronic brain injuries, these ion transporters can be activated and differentially regulate glial functions, which has subsequent impact on brain injury or tissue repair and functional recovery. In this review, we summarized the current knowledge about major glial ion transporters, including Na /H exchangers (NHE), Na /Ca exchangers (NCX), Na -K -Cl cotransporters (NKCC), and Na -HCO cotransporters (NBC). In acute neurological diseases, such as ischemic stroke and traumatic brain injury (TBI), these ion transporters are rapidly activated and play significant roles in regulation of the intra- and extracellular pH, Na , K , and Ca homeostasis, synaptic plasticity, and myelin formation. However, overstimulation of these ion transporters can contribute to glial apoptosis, demyelination, inflammation, and excitotoxicity. In chronic brain diseases, such as glioma, Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS), glial ion transporters are involved in the glioma Warburg effect, glial activation, neuroinflammation, and neuronal damages. These findings suggest that glial ion transporters are involved in tissue structural and functional restoration, or brain injury and neurological disease development and progression. A better understanding of these ion transporters in acute and chronic neurological diseases will provide insights for their potential as therapeutic targets.
Topics: Animals; Brain; Brain Diseases; Homeostasis; Humans; Ion Transport; Neuroglia; Sodium-Hydrogen Exchangers
PubMed: 31418931
DOI: 10.1002/glia.23699