scholarly journals Reconstitution of CO2 regulation of SLAC1 anion channel and function of CO2-permeable PIP2;1 aquaporin as carbonic anhydrase 4 interactor

2015 ◽  
Author(s):  
Cun Wang ◽  
Honghong Hu ◽  
Xue Qin ◽  
Brian Zeise ◽  
Danyun Xu ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Xenopus Oocytes ◽  
Stomatal Closure ◽  
Anion Channel ◽  
Co2 Concentration ◽  
Bimolecular Fluorescence Complementation ◽  
Molecular Signaling ◽  
Carbonic Anhydrases ◽  
Ion Channel Regulation ◽  
Co2 Regulation

Daily dark periods cause an increase in the leaf CO2 concentration (Ci) and the continuing atmospheric [CO2] rise also increases Ci. Elevated Ci causes closing of stomatal pores thus regulating gas exchange of plants. The molecular signaling mechanisms leading to CO2-induced stomatal closure are only partially understood. Here we demonstrate that high intracellular CO2/HCO3- enhances currents mediated by the guard cell S-type anion channel SLAC1 when co-expressing either of the protein kinases OST1, CPK6 or CPK23 in Xenopus oocytes. Split-ubiquitin screening identified the PIP2;1 aquaporin as an interactor of the βCA4 carbonic anhydrase, which was confirmed in split luciferase, bimolecular fluorescence complementation and co-immunoprecipitation experiments. PIP2;1 exhibited CO2 permeability. Co-expression of βCA4 and PIP2;1 with OST1-SLAC1 or CPK6/23-SLAC1 enabled extracellular CO2 enhancement of SLAC1 anion channel activity. An inactive PIP2;1 point mutation was identified which abrogated water and CO2 permeability and extracellular CO2 regulation of SLAC1 activity in Xenopus oocytes. These findings identify the CO2-permeable PIP2;1 aquaporin as key interactor of carbonic anhydrases, show functional reconstitution of extracellular CO2 signaling to ion channel regulation and implicate SLAC1 as a bicarbonate-responsive protein in CO2 regulation of S-type anion channels.

Are Carbonic Anhydrases Suitable Targets to Fight Protozoan Parasitic Diseases?

2019 ◽  
Vol 25 (39) ◽  
pp. 5266-5278 ◽  
Author(s):  
Katia D'Ambrosio ◽  
Claudiu T. Supuran ◽  
Giuseppina De Simone
Keyword(s):  
Drug Resistance ◽  
Animal Models ◽  
Carbonic Anhydrase ◽  
Drug Target ◽  
Treatment Options ◽  
Parasitic Diseases ◽  
Carbonic Anhydrases ◽  
Extensive Drug Resistance ◽  
Protozoan Infections

Protozoans belonging to Plasmodium, Leishmania and Trypanosoma genera provoke widespread parasitic diseases with few treatment options and many of the clinically used drugs experiencing an extensive drug resistance phenomenon. In the last several years, the metalloenzyme Carbonic Anhydrase (CA, EC 4.2.1.1) was cloned and characterized in the genome of these protozoa, with the aim to search for a new drug target for fighting malaria, leishmaniasis and Chagas disease. P. falciparum encodes for a CA (PfCA) belonging to a novel genetic family, the η-CA class, L. donovani chagasi for a β-CA (LdcCA), whereas T. cruzi genome contains an α-CA (TcCA). These three enzymes were characterized in detail and a number of in vitro potent and selective inhibitors belonging to the sulfonamide, thiol, dithiocarbamate and hydroxamate classes were discovered. Some of these inhibitors were also effective in cell cultures and animal models of protozoan infections, making them of considerable interest for the development of new antiprotozoan drugs with a novel mechanism of action.

scholarly journals Synthesis and Human Carbonic Anhydrase I, II, IX, and XII Inhibition Studies of Sulphonamides Incorporating Mono-, Bi- and Tricyclic Imide Moieties

2021 ◽  
Vol 14 (7) ◽  
pp. 693
Author(s):  
Kalyan K. Sethi ◽  
KM Abha Mishra ◽  
Saurabh M. Verma ◽  
Daniela Vullo ◽  
Fabrizio Carta ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Carbonic Anhydrase ◽  
Docking Studies ◽  
Carbonic Anhydrases ◽  
Molecular Docking Studies ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Carbonic Anhydrase I ◽  
Human Carbonic Anhydrase ◽  
Inhibition Studies

New derivatives were synthesised by reaction of amino-containing aromatic sulphonamides with mono-, bi-, and tricyclic anhydrides. These sulphonamides were investigated as human carbonic anhydrases (hCAs, EC 4.2.1.1) I, II, IX, and XII inhibitors. hCA I was inhibited with inhibition constants (Kis) ranging from 49 to >10,000 nM. The physiologically dominant hCA II was significantly inhibited by most of the sulphonamide with the Kis ranging between 2.4 and 4515 nM. hCA IX and hCA XII were inhibited by these sulphonamides in the range of 9.7 to 7766 nM and 14 to 316 nM, respectively. The structure–activity relationships (SAR) are rationalised with the help of molecular docking studies.

Polypharmacology of epacadostat: a potent and selective inhibitor of the tumor associated carbonic anhydrases IX and XII

2019 ◽  
Vol 55 (40) ◽  
pp. 5720-5723 ◽  
Author(s):  
Andrea Angeli ◽  
Marta Ferraroni ◽  
Alessio Nocentini ◽  
Silvia Selleri ◽  
Paola Gratteri ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Selective Inhibitor ◽  
Carbonic Anhydrase Inhibitor ◽  
Carbonic Anhydrases ◽  
Indoleamine 2,3 Dioxygenase

Epacadostat (EPA), a selective indoleamine-2,3-dioxygenase 1 (IDO1) inhibitor, has been investigatedin vitroas a human (h) Carbonic Anhydrase Inhibitor (CAI).

scholarly journals Carbonic Anhydrases in Photosynthesizing Cells of C3 Higher Plants

Metabolites ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 73 ◽  
Author(s):  
Lyudmila Ignatova ◽  
Natalia Rudenko ◽  
Elena Zhurikova ◽  
Maria Borisova-Mubarakshina ◽  
Boris Ivanov
Keyword(s):  
Plasma Membrane ◽  
Carbonic Anhydrase ◽  
Environmental Conditions ◽  
Organic Molecules ◽  
Higher Plants ◽  
C3 Plants ◽  
Coherent System ◽  
Carbonic Anhydrases ◽  
Chloroplast Stroma ◽  
Different Parts

The review presents data on the location, nature, properties, number, and expression of carbonic anhydrase genes in the photosynthesizing cells of C3 plants. The available data about the presence of carbonic anhydrases in plasma membrane, cytoplasm, mitochondria, chloroplast stroma and thylakoids are scrutinized. Special attention was paid to the presence of carbonic anhydrase activities in the different parts of thylakoids, and on collation of sources of these activities with enzymes encoded by the established genes of carbonic anhydrases. The data are presented to show that the consistent incorporation of carbonic anhydrases belonging to different families of these enzymes forms a coherent system of CO2 molecules transport from air to chloroplasts in photosynthesizing cells, where they are included in organic molecules in the carboxylation reaction. It is discussed that the manifestation of the activity of a certain carbonic anhydrase depends on environmental conditions and the stage of ontogenesis.

Modulation of frequency and height of cytosolic calcium spikes by plasma membrane anion channels in guard cells

2021 ◽  
Author(s):  
Md Tahjib-Ul-Arif ◽  
Shintaro Munemasa ◽  
Toshiyuki Nakamura ◽  
Yoshimasa Nakamura ◽  
Yoshiyuki Murata
Keyword(s):  
Plasma Membrane ◽  
Stomatal Closure ◽  
Anion Channel ◽  
Guard Cells ◽  
Cytosolic Calcium ◽  
Peak Height ◽  
Extracellular Calcium ◽  
Wild Type ◽  
Anion Channels ◽  
In The Wild

Abstract Cytosolic calcium ([Ca2+]cyt) elevation activates plasma membrane anion channels in guard cells, which is required for stomatal closure. However, involvement of the anion channels in the [Ca2+]cyt elevation remains unclear. We investigated the involvement using Arabidopsis thaliana anion channel mutants, slac1-4 slah3-3 and slac1-4 almt12-1. Extracellular calcium induced stomatal closure in the wild-type plants but not in the anion channel mutant plants whereas extracellular calcium induced [Ca2+]cyt elevation both in the wild-type guard cells and in the mutant guard cells. The peak height and the number of the [Ca2+]cyt spike were lower and larger in the slac1-4 slah3-3 than in the wild-type and the height and the number in the slac1-4 almt12-1 were much lower and much larger than in the wild-type. These results suggest that the anion channels are involved in the regulation of [Ca2+]cyt elevation in guard cells.

Effect of PCMBS on CO2permeability of Xenopus oocytes expressing aquaporin 1 or its C189S mutant

1998 ◽  
Vol 275 (6) ◽  
pp. C1481-C1486 ◽  
Author(s):  
Gordon J. Cooper ◽  
Walter F. Boron
Keyword(s):  
Carbonic Anhydrase ◽  
Intracellular Ph ◽  
Xenopus Oocytes ◽  
Membrane Lipid ◽  
Wild Type ◽  
Aquaporin 1 ◽  
Gas Channel ◽  
A Cell ◽  
Pass Through ◽  
Rule Out

A recent study on Xenopus oocytes [N. L. Nakhoul, M. F. Romero, B. A. Davis, and W. F. Boron. Am. J. Physiol. 274 ( Cell Physiol. 43): C543–548, 1998] injected with carbonic anhydrase showed that expressing aquaporin 1 (AQP1) increases by ∼40% the rate at which exposing the cell to CO2 causes intracellular pH to fall. This observation is consistent with several interpretations. Overexpressing AQP1 might increase apparent CO2 permeability by 1) allowing CO2 to pass through AQP1, 2) stimulating injected carbonic anhydrase, 3) enhancing the CO2 solubility of the membrane’s lipid, or 4) increasing the expression of a native “gas channel.” The purpose of the present study was to distinguish among these possibilities. We found that expressing the H2O channel AQP1 in Xenopus oocytes increases the CO2 permeability of oocytes in an expression-dependent fashion, whereas expressing the K+ channel ROMK1 has no effect. The mercury derivative p-chloromercuriphenylsulfonic acid (PCMBS), which inhibits the H2O movement through AQP1, also blocks the AQP1-dependent increase in CO2 permeability. The mercury-insensitive C189S mutant of AQP1 increases the CO2 permeability of the oocyte to the same extent as does the wild-type channel. However, the C189S-dependent increase in CO2permeability is unaffected by treatment with PCMBS. These data rule out options 2–4 listed above. Thus our results suggest that CO2passes through the pore of AQP1 and are the first data to demonstrate that a gas can enter a cell by a means other than diffusing through the membrane lipid.

scholarly journals Polymorphisms in Brucella Carbonic anhydrase II mediate CO2 dependence and fitness in vivo

2019 ◽  
Author(s):  
JM García-Lobo ◽  
Y Ortiz ◽  
C González-Riancho ◽  
A Seoane ◽  
B Arellano-Reynoso ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Primary Cultures ◽  
Low Frequency ◽  
Carbonic Anhydrase Ii ◽  
Carbonic Anhydrases ◽  
Significant Difference ◽  
Dependent Strain

AbstractSome Brucella isolates are known to require an increased concentration of CO2 for growth, especially in the case of primary cultures obtained directly from infected animals. Moreover, the different Brucella species and biovars show a characteristic pattern of CO2 requirement, and this trait has been included among the routine typing tests used for species and biovar differentiation. By comparing the differences in gene content among different CO2-dependent and CO2-independent Brucella strains we have confirmed that carbonic anhydrase II (CA II), is the enzyme responsible for this phenotype in all the Brucella strains tested. Brucella species contain two carbonic anhydrases of the β family, CA I and CA II; genetic polymorphisms exist for both of them in different isolates, but only those putatively affecting the activity of CA II correlate with the CO2 requirement of the corresponding isolate. Analysis of these polymorphisms does not allow the determination of CA I functionality, while the polymorphisms in CA II consist of small deletions that cause a frameshift that changes the C-terminus of the protein, probably affecting its dimerization status, essential for the activity.CO2-independent mutants arise easily in vitro, although with a low frequency ranging from 10−6 to 10−10 depending on the strain. These mutants carry compensatory mutations that produce a full length CA II. At the same time, no change was observed in the sequence coding for CA I. A competitive index assay designed to evaluate the fitness of a CO2-dependent strain compared to its corresponding CO2-independent strain revealed that while there is no significant difference when the bacteria are grown in culture plates, growth in vivo in a mouse model of infection provides a significant advantage to the CO2-dependent strain. This could explain why some Brucella isolates are CO2-dependent in primary isolation. The polymorphism described here also allows the in silico determination of the CO2 requirement status of any Brucella strain.

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