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Infection and Immunity Mar 2021Host colonization by a pathogen requires proper sensing and response to local environmental cues, to ensure adaptation and continued survival within the host. The ionic... (Review)
Review
Host colonization by a pathogen requires proper sensing and response to local environmental cues, to ensure adaptation and continued survival within the host. The ionic milieu represents a critical potential source of environmental cues, and indeed, there has been extensive study of the interplay between host and pathogen in the context of metals such as iron, zinc, and manganese, vital ions that are actively sequestered by the host. The inherent non-uniformity of the ionic milieu also extends, however, to "abundant" ions such as chloride and potassium, whose concentrations vary greatly between tissue and cellular locations, and with the immune response. Despite this, the concept of abundant ions as environmental cues and key players in host-pathogen interactions is only just emerging. Focusing on chloride and potassium, this review brings together studies across multiple bacterial and parasitic species that have begun to define both how these abundant ions are exploited as cues during host infection, and how they can be actively manipulated by pathogens during host colonization. The close links between ion homeostasis and sensing/response to different ionic signals, and the importance of studying pathogen response to cues in combination, are also discussed, while considering the fundamental insight still to be uncovered from further studies in this nascent area of inquiry.
Topics: Animals; Anions; Bacteria; Chlorides; Disease Susceptibility; Homeostasis; Host-Parasite Interactions; Host-Pathogen Interactions; Humans; Ions; Potassium
PubMed: 33526568
DOI: 10.1128/IAI.00641-20 -
Physiologia Plantarum Apr 2021High salinity induces osmotic stress and often leads to sodium ion-specific toxicity, with inhibitory effects on physiological, biochemical and developmental pathways.... (Review)
Review
High salinity induces osmotic stress and often leads to sodium ion-specific toxicity, with inhibitory effects on physiological, biochemical and developmental pathways. To cope with increased Na in soil water, plants restrict influx, compartmentalize ions into vacuoles, export excess Na from the cell, and distribute ions between the aerial and root organs. In this review, we discuss our current understanding of how high-affinity K transporters (HKT) contribute to salinity tolerance, focusing on HKT1-like family members primarily involved in long-distance transport, and in the recent research in the model plant Arabidopsis and its halophytic counterparts of the Eutrema genus. Functional characterization of the salt overly sensitive (SOS) pathway and HKT1-type transporters in these species indicate that they utilize similar approaches to deal with salinity, regardless of their tolerance.
Topics: Arabidopsis; Cation Transport Proteins; Ions; Plant Proteins; Potassium; Salt-Tolerant Plants; Sodium
PubMed: 32652584
DOI: 10.1111/ppl.13166 -
Biochimica Et Biophysica Acta Oct 2016The voltage dependent anion-selective channel, VDAC, is the major permeability pathway by which molecules and ion cross the mitochondrial outer membrane. This pathway... (Review)
Review
The voltage dependent anion-selective channel, VDAC, is the major permeability pathway by which molecules and ion cross the mitochondrial outer membrane. This pathway has evolved to optimize the flow of these substances and to control this flow by a gating process that is influenced by a variety of factors including transmembrane voltage. The permeation pathway formed through the membrane by VDAC is complex. Small ion flow is primarily influenced by the charged surface of the inner walls of the channel. Channel closure changes this landscape resulting in a change from a channel that favors anions to one that favors cations. Molecular ions interact more intimately with the inner walls of the channel and are selected by their 3-dimensional structure, not merely by their size and charge. Molecular ions typically found in cells are greatly favored over those that are not. For these larger structures the channel may form a low-energy translocation path that complements the structure of the permeant. This article is part of a Special Issue entitled: Mitochondrial Channels edited by Pierre Sonveaux, Pierre Maechler and Jean-Claude Martinou.
Topics: Adenosine Triphosphate; Animals; Biological Transport, Active; Chlorides; Humans; Ion Channel Gating; Ion Transport; Mitochondrial Membranes; Models, Molecular; Potassium; Protein Conformation; Static Electricity; Structure-Activity Relationship; Substrate Specificity; Voltage-Dependent Anion Channels
PubMed: 26826035
DOI: 10.1016/j.bbamcr.2016.01.019 -
Biomedicine & Pharmacotherapy =... Feb 2023Metabolic acidosis is frequent in chronic kidney disease (CKD) and is associated with accelerated progression of CKD, hypercatabolism, bone disease, hyperkalemia, and... (Review)
Review
Metabolic acidosis is frequent in chronic kidney disease (CKD) and is associated with accelerated progression of CKD, hypercatabolism, bone disease, hyperkalemia, and mortality. Clinical guidelines recommend a target serum bicarbonate ≥ 22 mmol/L, but metabolic acidosis frequently remains undiagnosed and untreated. Sodium zirconium cyclosilicate (SZC) binds potassium in the gut and is approved to treat hyperkalemia. In clinical trials with a primary endpoint of serum potassium, SZC increased serum bicarbonate, thus treating CKD-associated metabolic acidosis. The increase in serum bicarbonate was larger in patients with more severe pre-existent metabolic acidosis, was associated to decreased serum urea and was maintained for over a year of SZC therapy. SZC also decreased serum urea and increased serum bicarbonate after switching from a potassium-binding resin in normokalemic individuals. Mechanistically, these findings are consistent with SZC binding the ammonium ion (NH) generated from urea by gut microbial urease, preventing its absorption and, thus, preventing the liver regeneration of urea and promoting the fecal excretion of H. This mechanism of action may potentially result in benefits dependent on corrected metabolic acidosis (e.g., improved well-being, decreased catabolism, improved CKD mineral bone disorder, better control of serum phosphate, slower progression of CKD) and dependent on lower urea levels, such as decreased protein carbamylation. A roadmap is provided to guide research into the mechanisms and clinical consequences of the impact of SZC on serum bicarbonate and urate.
Topics: Humans; Hyperkalemia; Bicarbonates; Acidosis; Potassium; Renal Insufficiency, Chronic
PubMed: 36916426
DOI: 10.1016/j.biopha.2022.114197 -
Annual Review of Plant Biology 2015Mechanosensitive (MS) ion channels are a common mechanism for perceiving and responding to mechanical force. This class of mechanoreceptors is capable of transducing... (Review)
Review
Mechanosensitive (MS) ion channels are a common mechanism for perceiving and responding to mechanical force. This class of mechanoreceptors is capable of transducing membrane tension directly into ion flux. In plant systems, MS ion channels have been proposed to play a wide array of roles, from the perception of touch and gravity to the osmotic homeostasis of intracellular organelles. Three families of plant MS ion channels have been identified: the MscS-like (MSL), Mid1-complementing activity (MCA), and two-pore potassium (TPK) families. Channels from these families vary widely in structure and function, localize to multiple cellular compartments, and conduct chloride, calcium, and/or potassium ions. However, they are still likely to represent only a fraction of the MS ion channel diversity in plant systems.
Topics: Calcium; Ion Channels; Ion Transport; Mechanotransduction, Cellular; Plant Proteins; Plants; Potassium
PubMed: 25494462
DOI: 10.1146/annurev-arplant-043014-114700 -
Nature Communications Jun 2023Cyclic di-AMP is the only known essential second messenger in bacteria and archaea, regulating different proteins indispensable for numerous physiological processes. In...
Cyclic di-AMP is the only known essential second messenger in bacteria and archaea, regulating different proteins indispensable for numerous physiological processes. In particular, it controls various potassium and osmolyte transporters involved in osmoregulation. In Bacillus subtilis, the K/H symporter KimA of the KUP family is inactivated by c-di-AMP. KimA sustains survival at potassium limitation at low external pH by mediating potassium ion uptake. However, at elevated intracellular K concentrations, further K accumulation would be toxic. In this study, we reveal the molecular basis of how c-di-AMP binding inhibits KimA. We report cryo-EM structures of KimA with bound c-di-AMP in detergent solution and reconstituted in amphipols. By combining structural data with functional assays and molecular dynamics simulations we reveal how c-di-AMP modulates transport. We show that an intracellular loop in the transmembrane domain interacts with c-di-AMP bound to the adjacent cytosolic domain. This reduces the mobility of transmembrane helices at the cytosolic side of the K binding site and therefore traps KimA in an inward-occluded conformation.
Topics: Cyclic AMP; Protons; Bacterial Proteins; Second Messenger Systems; Membrane Transport Proteins; Potassium; Dinucleoside Phosphates
PubMed: 37344476
DOI: 10.1038/s41467-023-38944-1 -
International Journal of Molecular... May 2021Transport of ions and nutrients is a core mitochondrial function, without which there would be no mitochondrial metabolism and ATP production. Both ion homeostasis and... (Review)
Review
Transport of ions and nutrients is a core mitochondrial function, without which there would be no mitochondrial metabolism and ATP production. Both ion homeostasis and mitochondrial phenotype undergo pervasive changes during cancer development, and both play key roles in driving the malignancy. However, the link between these events has been largely ignored. This review comprehensively summarizes and critically discusses the role of the reciprocal relationship between ion transport and mitochondria in crucial cellular functions, including metabolism, signaling, and cell fate decisions. We focus on Ca, H, and K, which play essential and highly interconnected roles in mitochondrial function and are profoundly dysregulated in cancer. We describe the transport and roles of these ions in normal mitochondria, summarize the changes occurring during cancer development, and discuss how they might impact tumorigenesis.
Topics: Calcium; Cell Movement; Cell Proliferation; Homeostasis; Humans; Ion Channels; Ion Transport; Mitochondria; Neoplasms; Neoplastic Stem Cells; Potassium; Protons; Tumor Microenvironment
PubMed: 34069047
DOI: 10.3390/ijms22105209 -
Analytical Chemistry Aug 2017Ion-selective optodes (ISOs), the optical analog of ion-selective electrodes, have played an increasingly important role in chemical and biochemical analysis. Here we...
Ion-selective optodes (ISOs), the optical analog of ion-selective electrodes, have played an increasingly important role in chemical and biochemical analysis. Here we extend this technique to ion-selective photoacoustic optodes (ISPAOs) that serve at the same time as fluorescence-based ISOs, and apply it specifically to potassium (K). Notably, the potassium ion is one of the most abundant cations in biological systems, involved in numerous physiological and pathological processes. Furthermore, it has been recently reported that the presence of abnormal extracellular potassium concentrations in tumors suppresses the immune responses and thus suppresses immunotherapy. However, unfortunately, sensors capable of providing potassium images in vivo are still a future proposition. Here, we prepared an ion-selective potassium nanosensor (NS) aimed at in vivo photoacoustic (PA) chemical imaging of the extracellular environment, while being also capable of fluorescence based intracellular ion-selective imaging. This potassium nanosensor (K NS) modulates its optical properties (absorbance and fluorescence) according to the potassium concentration. The K NS is capable of measuring potassium, in the range of 1 mM to 100 mM, with high sensitivity and selectivity, by ISPAO based measurements. Also, a near infrared dye surface modified K NS allows fluorescence-based potassium sensing in the range of 20 mM to 1 M. The K NS serves thus as both PA and fluorescence based nanosensor, with response across the biologically relevant K concentrations, from the extracellular 5 mM typical values (through PA imaging) to the intracellular 150 mM typical values (through fluorescence imaging).
Topics: Amines; Cations; Fluorescent Dyes; HeLa Cells; Humans; Ion-Selective Electrodes; Micelles; Microscopy, Fluorescence; Nanostructures; Photoacoustic Techniques; Poloxamer; Potassium
PubMed: 28633520
DOI: 10.1021/acs.analchem.7b00930 -
The Journal of General Physiology Oct 2016Ion channels are membrane proteins that mediate efficient ion transport across the hydrophobic core of cell membranes, an unlikely process in their absence. K(+)... (Review)
Review
Ion channels are membrane proteins that mediate efficient ion transport across the hydrophobic core of cell membranes, an unlikely process in their absence. K(+) channels discriminate K(+) over cations with similar radii with extraordinary selectivity and display a wide diversity of ion transport rates, covering differences of two orders of magnitude in unitary conductance. The pore domains of large- and small-conductance K(+) channels share a general architectural design comprising a conserved narrow selectivity filter, which forms intimate interactions with permeant ions, flanked by two wider vestibules toward the internal and external openings. In large-conductance K(+) channels, the inner vestibule is wide, whereas in small-conductance channels it is narrow. Here we raise the idea that the physical dimensions of the hydrophobic internal vestibule limit ion transport in K(+) channels, accounting for their diversity in unitary conductance.
Topics: Ion Transport; Models, Molecular; Potassium; Potassium Channels; Protein Conformation
PubMed: 27619418
DOI: 10.1085/jgp.201611625 -
Journal of Molecular Biology Aug 2021Potassium channels play critical roles in many physiological processes, providing a selective permeation route for K ions in and out of a cell, by employing a carefully... (Review)
Review
Potassium channels play critical roles in many physiological processes, providing a selective permeation route for K ions in and out of a cell, by employing a carefully designed selectivity filter, evolutionarily conserved from viruses to mammals. The structure of the selectivity filter was determined at atomic resolution by x-ray crystallography, showing a tight coordination of desolvated K ions by the channel. However, the molecular mechanism of K ions permeation through potassium channels remains unclear, with structural, functional and computational studies often providing conflicting data and interpretations. In this review, we will present the proposed mechanisms, discuss their origins, and will critically assess them against all available data. General properties shared by all potassium channels are introduced first, followed by the introduction of two main mechanisms of ion permeation: soft and direct knock-on. Then, we will discuss critical computational and experimental studies that shaped the field. We will especially focus on molecular dynamics (MD) simulations, that provided mechanistic and energetic aspects of K permeation, but at the same time created long-standing controversies. Further challenges and possible solutions are presented as well.
Topics: Humans; Ion Channel Gating; Molecular Dynamics Simulation; Permeability; Potassium; Potassium Channels
PubMed: 33891905
DOI: 10.1016/j.jmb.2021.167002