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https://www.readbyqxmd.com/read/27170636/with-no-lysine-l-wnk1-isoforms-are-negative-regulators-of-the-k-cl-cotransporters
#1
Adriana Mercado, Paola de Los Heros, Zesergio Melo, María Chávez-Canales, Adrián R Murillo-de-Ozores, Erika Moreno, Silvana Bazúa-Valenti, Norma Vázquez, Juliette Hadchouel, Gerardo Gamba
The K(+)-Cl(-) cotransporters (KCC1-KCC4) encompass a branch of the SLC12 family of electroneutral cation-coupled chloride cotransporters that translocate ions out of the cell to regulate various factors, including cell volume and intracellular chloride concentration, among others. L-WNK1 is an ubiquitously expressed kinase that is activated in response to osmotic stress and intracellular chloride depletion, and it is implicated in two distinct hereditary syndromes: the renal disease pseudohypoaldosteronism type II (PHAII) and the neurological disease hereditary sensory neuropathy 2 (HSN2)...
July 1, 2016: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/26463820/a-glial-k-cl-cotransporter-modifies-temperature-evoked-dynamics-in-caenorhabditis-elegans-sensory-neurons
#2
A Yoshida, S Nakano, T Suzuki, K Ihara, T Higashiyama, I Mori
K(+) /Cl(-) cotransporters (KCCs) are known to be crucial in the control of neuronal electrochemical Cl(-) gradient. However, the role of these proteins in glial cells remains largely unexplored despite a number of studies showing expression of KCC proteins in glial cells of many species. Here, we show that the Caenorhabditis elegans K(+) /Cl(-) cotransporter KCC-3 is expressed in glial-like cells and regulates the thermosensory behavior through modifying temperature-evoked activity of a thermosensory neuron...
April 2016: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/26142773/k-cl-cotransporters-cell-volume-homeostasis-and-neurological-disease
#3
REVIEW
Kristopher T Kahle, Arjun R Khanna, Seth L Alper, Norma C Adragna, Peter K Lauf, Dandan Sun, Eric Delpire
K(+)-Cl(-) cotransporters (KCCs) were originally characterized as regulators of red blood cell (RBC) volume. Since then, four distinct KCCs have been cloned, and their importance for volume regulation has been demonstrated in other cell types. Genetic models of certain KCCs, such as KCC3, and their inhibitory WNK-STE20/SPS1-related proline/alanine-rich kinase (SPAK) serine-threonine kinases, have demonstrated the evolutionary necessity of these molecules for nervous system cell volume regulation, structure, and function, and their involvement in neurological disease...
August 2015: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/24960328/-pathophysiological-aspects-of-k-cl-cotransporters
#4
REVIEW
Adriana Mercado, Zesergio Melo
The K+:Cl- cotransporters or KCCs are membrane proteins that move K+ and Cl- ions across the membrane without changing the transmembrane potential. KCCs belong to the SLC12 (Solute Carrier Family 12) family of electroneutral cation-chloride cotransporters (CCC), and they are secondary active ion transporters because use the established gradients from the primary active transporter through the Na+/K+- ATPase. Although there are nine members identify in this family, up today only seven genes had been characterized...
March 2014: Revista de Investigación Clínica; Organo del Hospital de Enfermedades de la Nutrición
https://www.readbyqxmd.com/read/24393035/the-wnk-regulated-spak-osr1-kinases-directly-phosphorylate-and-inhibit-the-k-cl-co-transporters
#5
Paola de Los Heros, Dario R Alessi, Robert Gourlay, David G Campbell, Maria Deak, Thomas J Macartney, Kristopher T Kahle, Jinwei Zhang
Precise homoeostasis of the intracellular concentration of Cl- is achieved via the co-ordinated activities of the Cl- influx and efflux. We demonstrate that the WNK (WNK lysine-deficient protein kinase)-activated SPAK (SPS1-related proline/alanine-rich kinase)/OSR1 (oxidative stress-responsive kinase 1) known to directly phosphorylate and stimulate the N[K]CCs (Na+-K+ ion co-transporters), also promote inhibition of the KCCs (K+-Cl- co-transporters) by directly phosphorylating a recently described C-terminal threonine residue conserved in all KCC isoforms [Site-2 (Thr1048)]...
March 15, 2014: Biochemical Journal
https://www.readbyqxmd.com/read/24273324/evolution-of-the-cation-chloride-cotransporter-family-ancient-origins-gene-losses-and-subfunctionalization-through-duplication
#6
Anna-Maria Hartmann, David Tesch, Hans Gerd Nothwang, Olaf R P Bininda-Emonds
The cation chloride cotransporter (CCCs) family comprises of four subfamilies-K(+)-Cl(-) cotransporters (KCCs), Na(+)-K(+)-2Cl(-) cotransporters (NKCCs), and Na(+)-Cl(-) cotransporters (NCCs)-and possibly two additional members-CCC interacting protein (CIP1) and polyamine transporters (CCC9)-as well. Altogether, CCCs can play essential physiological roles in transepithelial ion reabsorption and secretion, cell volume regulation, and inhibitory neurotransmission and so are present across all domains of life...
February 2014: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/24043619/n-terminal-serine-dephosphorylation-is-required-for-kcc3-cotransporter-full-activation-by-cell-swelling
#7
Zesergio Melo, Paola de los Heros, Silvia Cruz-Rangel, Norma Vázquez, Norma A Bobadilla, Herminia Pasantes-Morales, Dario R Alessi, Adriana Mercado, Gerardo Gamba
The K(+):Cl(-) cotransporter (KCC) activity is modulated by phosphorylation/dephosphorylation processes. In isotonic conditions, KCCs are inactive and phosphorylated, whereas hypotonicity promotes their dephosphorylation and activation. Two phosphorylation sites (Thr-991 and Thr-1048) in KCC3 have been found to be critical for its regulation. However, here we show that the double mutant KCC3-T991A/T1048A could be further activated by hypotonicity, suggesting that additional phosphorylation site(s) are involved...
November 1, 2013: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/23593405/a-trafficking-deficient-mutant-of-kcc3-reveals-dominant-negative-effects-on-k-cl-cotransport-function
#8
Jinlong Ding, José Ponce-Coria, Eric Delpire
The K-Cl cotransporter (KCC) functions in maintaining chloride and volume homeostasis in a variety of cells. In the process of cloning the mouse KCC3 cDNA, we came across a cloning mutation (E289G) that rendered the cotransporter inactive in functional assays in Xenopus laevis oocytes. Through biochemical studies, we demonstrate that the mutant E289G cotransporter is glycosylation-deficient, does not move beyond the endoplasmic reticulum or the early Golgi, and thus fails to reach the plasma membrane. We establish through co-immunoprecipitation experiments that both wild-type and mutant KCC3 with KCC2 results in the formation of hetero-dimers...
2013: PloS One
https://www.readbyqxmd.com/read/23481459/n-ethylmaleimide-activates-a-cl-independent-component-of-k-flux-in-mouse-erythrocytes
#9
Boris E Shmukler, Ann Hsu, Jessica Alves, Marie Trudel, Marco B Rust, Christian A Hubner, Alicia Rivera, Seth L Alper
The K-Cl cotransporters (KCCs) of mouse erythrocytes exhibit higher basal activity than those of human erythrocytes, but are similarly activated by cell swelling, by hypertonic urea, and by staurosporine. However, the dramatic stimulation of human erythroid KCCs by N-ethylmaleimide (NEM) is obscured in mouse erythrocytes by a prominent NEM-stimulated K(+) efflux that lacks Cl(-)-dependence. The NEM-sensitivity of Cl(-)-independent K(+) efflux of mouse erythrocytes is lower than that of KCC. The genetically engineered absence of the K-Cl cotransporters KCC3 and KCC1 from mouse erythrocytes does not modify Cl(-)-independent K(+) efflux...
June 2013: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/22813581/k-cl-cotransporter-1-kcc1-negatively-regulates-ngf-induced-neurite-outgrowth-in-pc12-cells
#10
Hikaru Nagao, Ken-ichi Nakajima, Naomi Niisato, Ryuichi Hirota, Hideki Bando, Hirofumi Sakaguchi, Yasuo Hisa, Yoshinori Marunaka
Potassium chloride cotransporters (KCCs) mediate electroneutrally-coupled transport of K(+) and Cl(-), and play crucial roles in various cell functions including regulation of cell volume and homeostasis of cellular Cl(-)content. Four isoforms of KCCs (KCC1, 2, 3, and 4) have been identified. KCC1 is ubiquitously expressed, whereas KCC2 is mainly expressed in neuronal cells of central nervous system. KCC3 is highly expressed in heart, skeletal muscle, kidney, lung and placenta. KCC4 is mainly expressed in epithelial cells...
2012: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/22179001/wnk3-is-a-putative-chloride-sensing-kinase
#11
REVIEW
Diana Pacheco-Alvarez, Gerardo Gamba
The with-no-lysine kinase 3 (WNK3) is a serine/threonine kinase that modulates the activity of the electroneutral cation-coupled chloride cotransporters (CCC). Using the Xenopus laevis oocyte heterologous expression system, it has been shown that WNK3 activates the Na(+)-coupled chloride cotransporters NKCC1, NKCC2, and NCC and inhibits the K(+)-coupled chloride cotransporters KCC1 through KCC4. Interestingly, the effect of catalytically inactive WNK3 is opposite to that of wild type WNK3: inactive WNK3 inhibits NKCCs and activates KCCs...
2011: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/22152068/opposite-temperature-effect-on-transport-activity-of-kcc2-kcc4-and-n-k-ccs-in-hek-293-cells
#12
Anna-Maria Hartmann, Hans Gerd Nothwang
UNLABELLED: ABSTRACT: BACKGROUND: Cation chloride cotransporters play essential roles in many physiological processes such as volume regulation, transepithelial salt transport and setting the intracellular chloride concentration in neurons. They consist mainly of the inward transporters NCC, NKCC1, and NKCC2, and the outward transporters KCC1 to KCC4. To gain insight into regulatory and structure-function relationships, precise determination of their activity is required...
2011: BMC Research Notes
https://www.readbyqxmd.com/read/21911617/the-potassium-chloride-cotransporter-2-promotes-cervical-cancer-cell-migration-and-invasion-by-an-ion-transport-independent-mechanism
#13
Wei-Chun Wei, Colin J Akerman, Sarah E Newey, Jiliu Pan, Nicholas W V Clinch, Yves Jacob, Meng-Ru Shen, Robert J Wilkins, J Clive Ellory
K(+)-Cl(-) cotransporters (KCCs) play a fundamental role in epithelial cell function, both in the context of ionic homeostasis and also in cell morphology, cell division and locomotion. Unlike other ubiquitously expressed KCC isoforms, expression of KCC2 is widely considered to be restricted to neurons, where it is responsible for maintaining a low intracellular chloride concentration to drive hyperpolarising postsynaptic responses to the inhibitory neurotransmitters GABA and glycine. Here we report a novel finding that KCC2 is widely expressed in several human cancer cell lines including the cervical cancer cell line (SiHa)...
November 15, 2011: Journal of Physiology
https://www.readbyqxmd.com/read/21813871/role-of-an-apical-k-cl-cotransporter-in-urine-formation-by-renal-tubules-of-the-yellow-fever-mosquito-aedes-aegypti
#14
Peter M Piermarini, Rebecca M Hine, Matthew Schepel, Jeremy Miyauchi, Klaus W Beyenbach
The K,Cl cotransporters (KCCs) of the SLC12 superfamily play critical roles in the regulation of cell volume, concentrations of intracellular Cl(-), and epithelial transport in vertebrate tissues. To date, the role(s) of KCCs in the renal functions of mosquitoes and other insects is less clear. In the present study, we sought molecular and functional evidence for the presence of a KCC in renal (Malpighian) tubules of the mosquito Aedes aegypti. Using RT-PCR on Aedes Malpighian tubules, we identified five alternatively spliced partial cDNAs that encode putative SLC12-like KCCs...
November 2011: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/21733850/k-cl-cotransporter-gene-expression-during-human-and-murine-erythroid-differentiation
#15
Dao Pan, Theodosia A Kalfa, Daren Wang, Mary Risinger, Scott Crable, Anna Ottlinger, Sharat Chandra, David B Mount, Christian A Hübner, Robert S Franco, Clinton H Joiner
The K-Cl cotransporter (KCC) regulates red blood cell (RBC) volume, especially in reticulocytes. Western blot analysis of RBC membranes revealed KCC1, KCC3, and KCC4 proteins in mouse and human cells, with higher levels in reticulocytes. KCC content was higher in sickle versus normal RBC, but the correlation with reticulocyte count was poor, with inter-individual variability in KCC isoform ratios. Messenger RNA for each isoform was measured by real time RT-quantitative PCR. In human reticulocytes, KCC3a mRNA levels were consistently the highest, 1-7-fold higher than KCC4, the second most abundant species...
September 2, 2011: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/21628876/function-of-k%C3%A2-%C2%BA-cl%C3%A2-cotransporters-in-the-acid-secretory-mechanism-of-gastric-parietal-cells
#16
REVIEW
Takuto Fujii, Kyosuke Fujita, Noriaki Takeguchi, Hideki Sakai
Gastric proton pump (H⁺, K⁺-ATPase) secretes H⁺ of acid (HCl) via the luminal membrane of parietal cells. For the HCl secretion, Cl⁻- and K⁺-transporting proteins are required. Recent our studies have demonstrated that K⁺-Cl⁻ cotransporters (KCC3a and KCC4) are expressed in gastric parietal cells. KCC3a is associated with Na⁺, K⁺-ATPase in the basolateral membrane, and KCC4 is associated with H⁺, K⁺-ATPase in the apical canalicular membrane. This paper summarizes the functional association between KCCs and P-type ATPases and the contribution of these complexes to acid secretion in gastric parietal cells...
2011: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/21613606/similar-effects-of-all-wnk3-variants-on-slc12-cotransporters
#17
Silvia Cruz-Rangel, Zesergio Melo, Norma Vázquez, Patricia Meade, Norma A Bobadilla, Herminia Pasantes-Morales, Gerardo Gamba, Adriana Mercado
With-no-lysine kinase 3 (WNK3) is a member of a subfamily of serine/threonine kinases that modulate the activity of the electroneutral cation-coupled chloride cotransporters. WNK3 activates NKCC1/2 and NCC and inhibits the KCCs. Four splice variants are generated from the WNK3 gene. Our previous studies focused on the WNK3-18a variant. However, it has been suggested that other variants could have different effects on the cotransporters. Thus, the present study was designed to define the effects of all WNK3 variants on members of the SLC12 family...
September 2011: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/21427702/two-types-of-chloride-transporters-are-required-for-gaba-a-receptor-mediated-inhibition-in-c-elegans
#18
Andrew Bellemer, Taku Hirata, Michael F Romero, Michael R Koelle
Chloride influx through GABA-gated Cl(-) channels, the principal mechanism for inhibiting neural activity in the brain, requires a Cl(-) gradient established in part by K(+)-Cl(-) cotransporters (KCCs). We screened for Caenorhabditis elegans mutants defective for inhibitory neurotransmission and identified mutations in ABTS-1, a Na(+)-driven Cl(-)-HCO(3)(-) exchanger that extrudes chloride from cells, like KCC-2, but also alkalinizes them. While animals lacking ABTS-1 or the K(+)-Cl(-) cotransporter KCC-2 display only mild behavioural defects, animals lacking both Cl(-) extruders are paralyzed...
May 4, 2011: EMBO Journal
https://www.readbyqxmd.com/read/20637866/phosphoregulation-of-the-na-k-2cl-and-k-cl-cotransporters-by-the-wnk-kinases
#19
REVIEW
Kristopher T Kahle, Jesse Rinehart, Richard P Lifton
Precise regulation of the intracellular concentration of chloride [Cl-]i is necessary for proper cell volume regulation, transepithelial transport, and GABA neurotransmission. The Na-K-2Cl (NKCCs) and K-Cl (KCCs) cotransporters, related SLC12A transporters mediating cellular chloride influx and efflux, respectively, are key determinants of [Cl-]i in numerous cell types, including red blood cells, epithelial cells, and neurons. A common "chloride/volume-sensitive kinase", or related system of kinases, has long been hypothesized to mediate the reciprocal but coordinated phosphoregulation of the NKCCs and the KCCs, but the identity of these kinase(s) has remained unknown...
December 2010: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/20516068/differences-in-the-large-extracellular-loop-between-the-k-cl-cotransporters-kcc2-and-kcc4
#20
Anna-Maria Hartmann, Meike Wenz, Adriana Mercado, Christof Störger, David B Mount, Eckhard Friauf, Hans Gerd Nothwang
K(+)Cl(-) cotransporters (KCCs) play fundamental physiological roles in processes such as inhibitory neurotransmission and cell volume regulation. Mammalian genomes encode four distinct KCC paralogs, which share basic transport characteristics but differ significantly in ion affinity, pharmacology, and relative sensitivity to cell volume. Studies to identify divergence in functional characteristics have thus far focused on the cytoplasmic termini. Here, we investigated sequence requirements of the large extracellular loop (LEL) for function in KCC2 and KCC4...
July 30, 2010: Journal of Biological Chemistry
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