Genomes and Genes
Gene Symbol: KCC3
Description: solute carrier family 12 member 6
Alias: ACCPN, KCC3, KCC3A, KCC3B, solute carrier family 12 member 6, K-Cl cotransporter 3, electroneutral potassium-chloride cotransporter 3, potassium chloride cotransporter 3, potassium chloride cotransporter KCC3a-S3, potassium-chloride transporter-3a, potassium-chloride transporter-3b, solute carrier family 12 (potassium/chloride transporter), member 6, solute carrier family 12 (potassium/chloride transporters), member 6
- Molecular cloning and functional characterization of KCC3, a new K-Cl cotransporterJ E Race
Renal Division, Department of Medicine, State University of New York Health Science Center, Syracuse 13210, New York
Am J Physiol 277:C1210-9. 1999We isolated and characterized a novel K-Cl cotransporter, KCC3, from human placenta. The deduced protein contains 1,150 amino acids...
- NH2-terminal heterogeneity in the KCC3 K+-Cl- cotransporterAdriana Mercado
Renal Division, Brigham and Women s Hospital, Boston, MA 02115, USA
Am J Physiol Renal Physiol 289:F1246-61. 2005..Two major isoforms, KCC3a and KCC3b, are generated by transcriptional initiation 5' of two distinct first coding exons...
- Axonal and periaxonal swelling precede peripheral neurodegeneration in KCC3 knockout miceNellie Byun
Neuroscience Graduate Program, Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, T 4202 MCN 1161 21st Avenue South, Nasvhille, TN 37232 2520, USA
Neurobiol Dis 28:39-51. 2007..in KCC3 knockout mice, an animal model of agenesis of the corpus callosum associated with peripheral neuropathy (ACCPN) [Howard, H.C., Mount, D.B., Rochefort, D., Byun, N., Dupre, N., Lu, J., Fan, X., Song, L., Riviere, J.B...
- A deletion mutation in Slc12a6 is associated with neuromuscular disease in gaxp miceYan Jiao
Department of Orthopaedic Surgery Campbell Clinic, University of Tennessee Health Science Center, Memphis, TN 38163, USA
Genomics 91:407-14. 2008..Western blot analysis indicated that the protein product of Slc12a6, the K(+)-Cl(-) cotransporter Kcc3, was not detectable in gaxp mice...
- Insulin-like growth factor 1 stimulates KCl cotransport, which is necessary for invasion and proliferation of cervical cancer and ovarian cancer cellsMeng Ru Shen
Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan
J Biol Chem 279:40017-25. 2004..Taken together, our results indicate that KCC activation by IGF-1 plays an important role in IGF-1 signaling to promote growth and spread of gynecological cancers...
- Cloning and characterization of KCC3 and KCC4, new members of the cation-chloride cotransporter gene familyD B Mount
Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
J Biol Chem 274:16355-62. 1999..We have cloned cDNAs encoding mouse KCC3, human KCC3, and human KCC4, three new members of this gene family...
- Novel truncating and missense mutations of the KCC3 gene associated with Andermann syndromeG Uyanik
Department of Neurology, University of Regensburg, Germany
Neurology 66:1044-8. 2006..The cerebral MRI reveals a variable degree of agenesis of the corpus callosum. Recently, truncating mutations of the KCC3 gene (also known as SLC12A6) have been associated with Andermann syndrome.
- KCl cotransporter-3 down-regulates E-cadherin/beta-catenin complex to promote epithelial-mesenchymal transitionYueh Mei Hsu
Institute of Basic Medical Sciences, Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
Cancer Res 67:11064-73. 2007..Real-time reverse transcription-PCR on the samples collected from the laser microdissection indicates that KCC3 is the most abundant KCC isoform in cervical carcinoma...
- Sites of regulated phosphorylation that control K-Cl cotransporter activityJesse Rinehart
Department of Genetics, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA
Cell 138:525-36. 2009..We identified two sites in KCC3 that are rapidly dephosphorylated in hypotonic conditions in cultured cells and human red blood cells in parallel ..
- Similar effects of all WNK3 variants on SLC12 cotransportersSilvia Cruz-Rangel
Departamento de Fisiología y Desarrollo Neural, Instituto de Fisiologia Celular, Universidad Nacional Autonoma de Mexico, Coyoacan, Mexico City, Mexico
Am J Physiol Cell Physiol 301:C601-8. 2011..That is, NKCC1/2 and NCC were inhibited, even in hypertonicity, while KCCs were activated, even in isotonic conditions. We conclude that the effects of all WNK3 variants toward SLC12 proteins are similar...
- Transit defect of potassium-chloride Co-transporter 3 is a major pathogenic mechanism in hereditary motor and sensory neuropathy with agenesis of the corpus callosumAdèle Salin-Cantegrel
Centre of Excellence in Neuromics, University of Montreal, Centre Hospitalier de L Universite de Montreal Research Center, Montreal, Quebec H2L 4M1, Canada
J Biol Chem 286:28456-65. 2011Missense and protein-truncating mutations of the human potassium-chloride co-transporter 3 gene (KCC3) cause hereditary motor and sensory neuropathy with agenesis of the corpus callosum (HMSN/ACC), which is a severe neurodegenerative ..
- The K-Cl cotransporter KCC3 is mutant in a severe peripheral neuropathy associated with agenesis of the corpus callosumHeidi C Howard
Centre for Research in Neuroscience, McGill University and The Montreal General Hospital Research Institute, 1650 Cedar Ave, Montreal, Quebec H3G 1A4, Canada
Nat Genet 32:384-92. 2002Peripheral neuropathy associated with agenesis of the corpus callosum (ACCPN) is a severe sensorimotor neuropathy associated with mental retardation, dysmorphic features and complete or partial agenesis of the corpus callosum...
- N-terminal serine dephosphorylation is required for KCC3 cotransporter full activation by cell swellingZesergio Melo
From the Molecular Physiology Unit, Instituto de Investigaciones Biomedicas, Universidad Nacional Autónoma de México and Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, 14000 Mexico City, Mexico
J Biol Chem 288:31468-76. 2013..Two phosphorylation sites (Thr-991 and Thr-1048) in KCC3 have been found to be critical for its regulation...
- Cation chloride cotransporters interact with the stress-related kinases Ste20-related proline-alanine-rich kinase (SPAK) and oxidative stress response 1 (OSR1)Kerstin Piechotta
Department of Anesthesiology and Center for Molecular Neuroscience, Vanderbilt University, Medical Center, Nashville, Tennessee 37232, USA
J Biol Chem 277:50812-9. 2002..Ste20-related proline-alanine-rich kinase (SPAK) and oxidative stress response 1 (OSR1) with the cotransporters KCC3, NKCC1, and NKCC2 but not KCC1 and KCC4...
- IGF-1 upregulates electroneutral K-Cl cotransporter KCC3 and KCC4 which are differentially required for breast cancer cell proliferation and invasivenessYueh Mei Hsu
Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan
J Cell Physiol 210:626-36. 2007..IGF-1 stimulates KCC activity of MCF-7 breast cancer cells in a dose- and time-dependent manner. Increased KCC3 and KCC4 abundances contribute to IGF-1-enhanced KCC activity...
- The WNK-regulated SPAK/OSR1 kinases directly phosphorylate and inhibit the K+-Cl- co-transportersPaola de los Heros
MRC Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, U K
Biochem J 458:559-73. 2014..Secondly, STOCK1S-50699, a WNK pathway inhibitor, suppresses SPAK/OSR1 activation and KCC3A Site-2 phosphorylation with similar efficiency...
- KCC3-dependent chloride extrusion in adult sensory neuronsOlivier Lucas
INSERM, U 1051, Institute for Neurosciences of Montpellier, Montpellier, F 34000, 80, rue Augustin Fliche, 34091 Montpellier Cedex 5, France
Mol Cell Neurosci 50:211-20. 2012..amounts than the other cation-Cl(-) cotransporter transcripts and RT-PCR shows larger expression of the shorter KCC3a isoform in adult DRG...
- K⁺-Cl⁻ cotransport mediates the bactericidal activity of neutrophils by regulating NADPH oxidase activationYuan Ting Sun
Institute of Clinical Medicine, National Cheng Kung University Hospital, Tainan 704, Taiwan
J Physiol 590:3231-43. 2012..Inhibition of KCC activity or knockdown of KCC expression, in particular KCC3, reduced the phosphorylation as well as the membrane recruitment of oxidase components...
- Loss of neuronal potassium/chloride cotransporter 3 (KCC3) is responsible for the degenerative phenotype in a conditional mouse model of hereditary motor and sensory neuropathy associated with agenesis of the corpus callosumMasoud Shekarabi
Center of Excellence in Neuroscience of the Université de Montréal, Centre de recherche du Centre Hospitalier de l Universite de Montreal, University of Montreal, Montreal, Quebec H2L 4MI, Canada
J Neurosci 32:3865-76. 2012Disruption of the potassium/chloride cotransporter 3 (KCC3), encoded by the SLC12A6 gene, causes hereditary motor and sensory neuropathy associated with agenesis of the corpus callosum (HMSN/ACC), a neurodevelopmental and ..
- K-Cl cotransporters, cell volume homeostasis, and neurological diseaseKristopher T Kahle
Department of Neurosurgery, Boston Children s Hospital and Harvard Medical School, Boston, MA 02114, USA Manton Center for Orphan Disease Research, Children s Hospital Boston, 300 Longwood Avenue, Boston, MA 02114, USA Electronic address
Trends Mol Med 21:513-23. 2015..Genetic models of certain KCCs, such as KCC3, and their inhibitory WNK-STE20/SPS1-related proline/alanine-rich kinase (SPAK) serine-threonine kinases, have ..
- ALS5/SPG11/KIAA1840 mutations cause autosomal recessive axonal Charcot-Marie-Tooth diseaseCeleste Montecchiani
1 Laboratorio di Neurogenetica, CERC IRCCS Santa Lucia, Rome, Italy
Brain 139:73-85. 2016..Our results indicate that ALS5/SPG11/KIAA1840 is the causative gene of a wide spectrum of clinical features, including autosomal recessive axonal Charcot-Marie-Tooth disease...
- Gain-of-function missense variant in SLC12A2, encoding the bumetanide-sensitive NKCC1 cotransporter, identified in human schizophreniaNancy D Merner
Harrison School of Pharmacy, Department of Drug Discovery and Development, Auburn University, Auburn, AL, USA
J Psychiatr Res 77:22-6. 2016..No NKCC1 variants were detected in ASD or ID, and no KCC3 variants were identified in any of the three neurodevelopmental disorder cohorts...
- Ablation of Potassium-Chloride Cotransporter Type 3 (Kcc3) in Mouse Causes Multiple Cardiovascular Defects and Isosmotic PolyuriaAlexandre P Garneau
Nephrology Research Group, Centre de Recherche L Hotel Dieu de Quebec, Centre Hospitalier Universitaire de Quebec, Quebec City, Canada
PLoS ONE 11:e0154398. 2016Inactivation of Kcc3 in a mixed 129/Sv×C57BL/6 mouse background has been previously found to increase systemic blood pressure (BP) through presumed neurogenic mechanisms...
- KCC3 deficiency-induced disruption of paranodal loops and impairment of axonal excitability in the peripheral nervous systemYuan Ting Sun
Department of Neurology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan Advanced Optoelectronic Technology Center, National Cheng Kung University, Tainan 704, Taiwan Department of Internal Medicine, National Cheng Kung University Hospital, Dou Liou Branch, Yun Lin 640, Taiwan
Neuroscience 335:91-102. 2016..of the Corpus Callosum (HMSN/ACC) is associated with the dysfunction of the K(+)-Cl(-) cotransporter type 3 (KCC3), which is an electroneutral cotransporter...
- [Molecular genetics of inherited neuropathies]Hiroshi Takashima
Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences
Rinsho Shinkeigaku 46:1-18. 2006..form), MFN2, KIF1B, RAB7, GARS, NEFL, HSPB1, HSPB8 for CMT2 (autosomal dominant axonal form); LMNA, GAN1, KCC3, TDP1, APTX, SETX for AR-CMT2 (autosomal recessive axonal form); GIB1 for CMTX (X-linked CMT); DNM2 for CMT-DI (..
- Functional kinomics establishes a critical node of volume-sensitive cation-Cl- cotransporter regulation in the mammalian brainJinwei Zhang
MRC Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland
Sci Rep 6:35986. 2016..and a kinase trapping-Orbitrap mass spectroscopy screen to systematically identify essential kinase regulators of KCC3 Thr991/Thr1048 phosphorylation - a key signaling event in cell swelling-induced regulatory ..
- The NO signaling pathway differentially regulates KCC3a and KCC3b mRNA expressionMauricio Di Fulvio
Department of Pharmacology and Toxicology, Wright State University, School of Medicine, 3640 Colonel Glenn Highway, Biological Sciences Building, Room 152 6, Dayton, OH 45435 0002, USA
Nitric Oxide 9:165-71. 2003..we report the presence, relative abundance, and regulation by sodium nitroprusside (SNP) of the novel KCC3a and KCC3b mRNAs, in primary cultures of rat VSMCs...
- Fine mapping the candidate region for peripheral neuropathy with or without agenesis of the corpus callosum in the French Canadian populationHeidi C Howard
Centre for Research in Neuroscience, Montreal General Hospital, Montreal, Quebec, Canada
Eur J Hum Genet 10:406-12. 2002Peripheral neuropathy with or without agenesis of the corpus callosum (ACCPN [MIM 2180000]) is an autosomal recessive disease characterised by progressive sensorimotor neuropathy, mental retardation, dysmorphic features and complete or ..
- Platelet-derived growth factor regulates K-Cl cotransport in vascular smooth muscle cellsJing Zhang
Department of Pharmacology and Toxicology and Physiology and Biophysics, Wright State University, School of Medicine, Dayton, Ohio 45435, USA
Am J Physiol Cell Physiol 284:C674-80. 2003..VSMCs possess K-Cl COT activity and the KCC1 and KCC3 isoforms...
- Aberrant chloride transport contributes to anoxic/ischemic white matter injurySameh A Malek
Ottawa Health Research Institute, Ottawa Hospital, University of Ottawa, Canada K1Y 4K9
J Neurosci 23:3826-36. 2003..Furosemide was also very effective at normalizing the shape of the CAPs. The KCC3a isoform was localized to astrocytes. KCC3 and weaker KCC3a was detected in myelin of larger axons...
- Differential expression pattern of chloride transporters NCC, NKCC2, KCC1, KCC3, KCC4, and AE3 in the developing rat auditory brainstemMichael Becker
Abteilung Tierphysiologie, Universitat Kaiserslautern, Kaiserslautern, Germany
Cell Tissue Res 312:155-65. 2003..Here we examined the expression of six secondary active chloride transporter genes ( NCC, NKCC2, KCC1, KCC3, KCC4, and AE3) in the rat SOC to unravel the molecular mechanisms underlying this change...
- Electroneutral cation-chloride cotransporters in the central nervous systemAdriana Mercado
Renal Division, Brigham and Women s Hospital and VA Boston Healthcare System, Harvard Medical School, 4 Blackfan Circle, Boston, Massachusetts, USA
Neurochem Res 29:17-25. 2004..Finally, the association between loss of function in the K+-Cl- cotransporter KCC3, with a severe peripheral neuropathy associated with agenesis of the corpus callosum, has revealed an unexpected ..
- Raising cytosolic Cl- in cerebellar granule cells affects their excitability and vestibulo-ocular learningPatricia Seja
Leibniz Institut für Molekulare Pharmakologie and Max Delbrück Centrum für Molekulare Medizin, Berlin, Germany
EMBO J 31:1217-30. 2012..In both GCs and PCs, disruption of Kcc2, but not Kcc3, increased [Cl(-)](i) roughly two-fold...
- Expanding the differential diagnosis of inherited neuropathies with non-uniform conduction: Andermann syndromeCharles M Lourenco
Department of Neurosciences and Behavior Neurosciences, School of Medicine of Ribeirao Preto, University of Sao Paulo, Av Bandeirantes 3900, Sao Paulo, Brazil
J Peripher Nerv Syst 17:123-7. 2012..A mutation was found on KCC3 gene, confirming Andermann syndrome, a disease that must be included in the differential diagnosis of inherited ..
- Basolateral Cl- transport is stimulated by terbutaline in adult rat alveolar epithelial cellsS Y Lee
Graduate Program in Molecular Veterinary Biosciences, University of Minnesota, MN 55108, USA
J Membr Biol 191:133-9. 2003..RT-PCR experiments detected mRNA for three KCl cotransport isoforms (KCC1, KCC3 and KCC4) in monolayer cultures of alveolar epithelial cells...
- Patterns of cation-chloride cotransporter expression during embryonic rodent CNS developmentHong Li
Institute of Biotechnology, PO Box 56, Viikinkaari 9C, FIN 00014 University of Helsinki, Finland
Eur J Neurosci 16:2358-70. 2002..b>KCC3 mRNA was scarce in the cortical plate at E14.5, and slightly up-regulated at birth...
- Role of cholesterol in functional association between K(+)-Cl(-) cotransporter-3a and Na+,K(+)-ATPaseKyosuke Fujita
Department of Pharmaceutical Physiology, University of Toyama, Toyama 930 0194, Japan
Biochem Biophys Res Commun 424:136-40. 2012K(+)-Cl(-) cotransporter-3a (KCC3a) is associated with Na(+),K(+)-ATPase α1-subunit (α1NaK) in lipid rafts of gastric acid-secreting cells and positively regulates Na(+),K(+)-ATPase activity...
- High-grade glioma motility reduced by genetic knockdown of KCC3Kenneth B Gagnon
Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, TN, USA
Cell Physiol Biochem 30:466-76. 2012..Genetic silencing of KCC3 with short hairpin interfering RNA reduced protein expression by 40 - 60%, K(+) influx by ~50%, and cell motility ..
- K(+)-Cl(-) cotransporter 1 (KCC1) negatively regulates NGF-induced neurite outgrowth in PC12 cellsHikaru Nagao
Department of Molecular Cell Physiology, Graduate School of Medical Science, Kyoto, Japan
Cell Physiol Biochem 30:538-51. 2012..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...
- Cation-chloride cotransporters in the nervous system: General features and clinical correlationsEduardo E Benarroch
From the Department of Neurology, Mayo Clinic, Rochester, MN
Neurology 80:756-63. 2013..the Na-K-2Cl cotransporter NKCC1, which mediates Cl(-) influx, and various K-Cl cotransporters, such as KCC2 and KCC3, that extrude Cl(-) from the cell...
- N-ethylmaleimide activates a Cl(-)-independent component of K(+) flux in mouse erythrocytesBoris E Shmukler
Divisions of Nephrology and Molecular and Vascular Medicine, Beth Israel Deaconess Medical Center, USA
Blood Cells Mol Dis 51:9-16. 2013..The genetically engineered absence of the K-Cl cotransporters KCC3 and KCC1 from mouse erythrocytes does not modify Cl(-)-independent K(+) efflux...
- A trafficking-deficient mutant of KCC3 reveals dominant-negative effects on K-Cl cotransport functionJinlong Ding
Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America
PLoS ONE 8:e61112. 2013..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 ..
- Potassium-chloride cotransporter 3 interacts with Vav2 to synchronize the cell volume decrease response with cell protrusion dynamicsAdèle Salin-Cantegrel
Centre of Excellence in Neuroscience of University of Montreal, Montreal, Quebec, Canada
PLoS ONE 8:e65294. 2013Loss-of-function of the potassium-chloride cotransporter 3 (KCC3) causes hereditary motor and sensory neuropathy with agenesis of the corpus callosum (HMSN/ACC), a severe neurodegenerative disease associated with defective midline ..
- Molecular evidence for a role for K(+)-Cl(-) cotransporters in the kidneyZesergio Melo
Molecular Physiology Unit, Vasco de Quiroga No 15, Tlalpan 14000, Mexico City, Mexico
Am J Physiol Renal Physiol 305:F1402-11. 2013K(+)-Cl(-) cotransporter (KCC) isoforms 3 (KCC3) and 4 (KCC4) are expressed at the basolateral membrane of proximal convoluted tubule cells, and KCC4 is present in the basolateral membrane of the thick ascending loop of Henle's limb and α..
- KCC isoforms in a human lens epithelial cell line (B3) and lens tissue extractsSandeep Misri
Cell Biophysics Group, Boonshoft School of Medicine, Wright State University, 054 Biological Sciences Building, Dayton, OH 45435, USA
Exp Eye Res 83:1287-94. 2006..spliced variants, RT-PCR with both rat and human primers revealed the predicted cDNA fragments of KCC1, KCC3a, KCC3b, and KCC4 but not KCC2 in both HLE-B3 cells and in human lens tissue extracts from cataractous patients...
- The role of potassium chloride cotransporters in murine and human sperm volume regulationT Klein
Institute of Reproductive Medicine, University of Munster, D 48129 Munster, Germany
Biol Reprod 75:853-8. 2006..Conventional RT-PCR indicated the presence of transcripts from Slc12a4 (KCC1), Slc12a6 (KCC3), and Slc12a7 (KCC4) in the testis, whereas RT-nested PCR revealed the latter two isoforms in sperm mRNA...
- Relative contribution of chloride channels and transporters to regulatory volume decrease in human glioma cellsNola Jean Ernest
Department of Neurobiology, University of Alabama at Birmingham, USA
Am J Physiol Cell Physiol 288:C1451-60. 2005..Finally, we identified several candidate proteins that may be involved in RVD, including the Cl(-) channels ClC-2, ClC-3, ClC-5, ClC-6, and ClC-7 and the transporters KCC1 and KCC3a.
- Hereditary motor and sensory neuropathy with agenesis of the corpus callosumNicolas Dupre
Centre for Research in Neurosciences and the Department of Neurology and Neurosurgery, McGill University, Montreal
Ann Neurol 54:9-18. 2003..and it is a protein-truncating mutation in the SLC12A6 gene, which codes for a cotransporter protein known as KCC3. Herein, we provide the first extensive review of this disorder, covering epidemiological, clinical, and molecular ..
- Thin corpus callosum and amyotrophy in spastic paraplegia--case report and review of literatureBeate Winner
Department of Neurology, University of Regensburg, Regensburg, Germany
Clin Neurol Neurosurg 108:692-8. 2006..Thin CC and peripheral neuropathy often appear together in spastic paraplegia and might be indicative for combined degeneration mechanism of central and peripheral axons...
- Knocking down of the KCC2 in rat hippocampal neurons increases intracellular chloride concentration and compromises neuronal survivalChristophe Pellegrino
INSERM Unité 901, Marseille, 13009, France
J Physiol 589:2475-96. 2011..The reparative effects of KCC2 were mimicked by over-expression of the KCC3, a homologue transporter...
- Volume regulation and KCl cotransport in reticulocyte populations of sickle and normal red blood cellsMaa Ohui Quarmyne
Division of Hematology, Cancer and Blood Diseases Institute, Cincinnati Children s Hospital Medical Center, USA
Blood Cells Mol Dis 47:95-9. 2011..We have shown previously that three of the four KCC genes - KCC1, KCC3, and KCC4 - are expressed in red blood cells (RBC) (Exp. Hem. 33:624, 2005)...
- Ammonium transport and pH regulation by K(+)-Cl(-) cotransportersMarc J Bergeron
Nephrology Group, Department of Medicine, Faculty of Medicine, Universite Laval, Quebec, Canada
Am J Physiol Renal Physiol 285:F68-78. 2003..Our results demonstrate that all of the CCCs examined (NKCC1, NKCC2, KCC1, KCC3, and KCC4) can promote NH4(+) translocation, presumably through binding of the ion at the K(+) site...
- Influence of K-Cl cotransporter activity on activation of volume-sensitive Cl- channels in human osteoblastsMargot Bräuer
Department of Applied Physiology, University of Ulm, 89081 Ulm, Germany
Am J Physiol Cell Physiol 285:C22-30. 2003....
- Function of K⁺-Cl⁻ cotransporters in the acid secretory mechanism of gastric parietal cellsTakuto Fujii
Department of Pharmaceutical Physiology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan
Biol Pharm Bull 34:810-2. 2011..Recent our studies have demonstrated that K⁺-Cl⁻ cotransporters (KCC3a and KCC4) are expressed in gastric parietal cells...
- K-Cl cotransporter gene expression during human and murine erythroid differentiationDao Pan
Molecular and Cell Therapy Program, Division of Experimental Hematology, Cincinnati Children s Hospital Medical Center, Cincinnati, Ohio 45229, USA
J Biol Chem 286:30492-503. 2011..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...
- KCC3 and KCC4 expression in rat adult forebrainP Le Rouzic
Faculty of Life Sciences, Stopford Building, Manchester, UK
Brain Res 1110:39-45. 2006..the widespread expression of KCC1 and KCC2 throughout the brain, we now show a more restricted expression of KCC3a in the hippocampus, choroid plexus and piriform cortex, as well as KCC4 in the choroid plexus and the ..
- Hereditary spastic paraplegia with thin corpus callosum: reduction of the SPG11 interval and evidence for further genetic heterogeneityAlexander Lossos
Department of Neurology, Agnes Ginges Center for Human Neurogenetics, Hadassah Hebrew University Medical Center, Jerusalem 91120, Israel
Arch Neurol 63:756-60. 2006..The locus for HSP-TCC, designated SPG11, was mapped to chromosome 15q13-15 in some of the affected families from Japan, Europe, and North America, spanning an interval of 17.5 megabases (Mb)...
- PASK (proline-alanine-rich STE20-related kinase), a regulatory kinase of the Na-K-Cl cotransporter (NKCC1)Brian F X Dowd
Yale University, School of Medicine, Department of Cellular and Molecular Physiology, New Haven, Connecticut 06520 0826, USA
J Biol Chem 278:27347-53. 2003..proline-alanine-rich kinase)) and OSR1 (oxidative stress response kinase) to cation-chloride cotransporters KCC3, NKCC1, and NKCC2...
- Neurogenic mechanisms contribute to hypertension in mice with disruption of the K-Cl cotransporter KCC3Marco B Rust
Zentrum fur Molekulare Neurobiologie Hamburg, Universitat Hamburg, Universitatsklinikum Hamburg Eppendorf, Hamburg, Germany
Circ Res 98:549-56. 2006The neurodegenerative disorder Andermann syndrome is caused by mutations of the K-Cl cotransporter KCC3. Mice with a targeted disruption of the corresponding gene, Slc12a6, reproduce neurodegeneration of the peripheral and central nervous ..
- Genetic factors underlying the risk of thalidomide-related neuropathy in patients with multiple myelomaDavid C Johnson
Institute of Cancer Research, London, UK
J Clin Oncol 29:797-804. 2011..To indentify genetic variation that can modulate and predict the risk of developing thalidomide-related peripheral neuropathy (TrPN)...
- Rare variants of the gene encoding the potassium chloride co-transporter 3 are associated with bipolar disorderJobst Meyer
Clinical and Molecular Psychobiology, Department of Psychiatry and Psychotherapy, University of Wuerzburg, Germany
Int J Neuropsychopharmacol 8:495-504. 2005..cause severe peripheral neuropathy frequently associated with agenesis of the corpus callosum and psychoses (ACCPN)...
- Loss of K-Cl co-transporter KCC3 causes deafness, neurodegeneration and reduced seizure thresholdThomas Boettger
Zentrum für Molekulare Neurobiologie, ZMNH, Universitat Hamburg, Falkenried 94, D 20251 Hamburg, Germany
EMBO J 22:5422-34. 2003..b>KCC3, an isoform mutated in the human Anderman syndrome, is expressed in brain, epithelia and other tissues...
- Chloride transport in the kidney: lessons from human disease and knockout miceThomas J Jentsch
Zentrum für Molekulare Neurobiologie ZMNH, Universitat Hamburg, Falkenried 94, D 20246 Hamburg, Germany
J Am Soc Nephrol 16:1549-61. 2005..Finally, both KCC3 and KCC4 are crucial for proximal tubular cell volume regulation.
- Regulation of K-Cl cotransport: from function to genesN C Adragna
Department of Pharmacology, Wright State University, School of Medicine, Dayton, OH 45435 0002, USA
J Membr Biol 201:109-37. 2004..A few reports indicate that the NO/cGMP/PKG signaling pathway regulates KCC1 and KCC3 mRNA expression in VSMCs at the post-transcriptional level...
- Expression of K+-Cl- cotransporters in the alpha-cells of rat endocrine pancreasSarah L Davies
School of Biological Sciences and Department of Medicine, University of Manchester, G 38 Stopford Building, Manchester M13 9PT, UK
Biochim Biophys Acta 1667:7-14. 2004The expression of K+-Cl- cotransporters (KCC) was examined in pancreatic islet cells. mRNA for KCC1, KCC3a, KCC3b and KCC4 were identified by RT-PCR in islets isolated from rat pancreas...
- K-Cl co-transport: immunocytochemical and functional evidence for more than one KCC isoform in high K and low K sheep erythrocytesP K Lauf
Department of Physiology and Biophysics, Wright State University, Dayton, OH 45435, USA
Comp Biochem Physiol A Mol Integr Physiol 130:499-509. 2001..anti-rat (rt)KCC1 antibodies against a fusion peptide with 77 amino acids from the Ctd of rtKCC1 and anti-human (h)KCC3 against an 18-aa peptide from the Ntd of hKCC3, were prepared in rabbits (rb)...
- Human and murine phenotypes associated with defects in cation-chloride cotransportEric Delpire
Department of Anesthesiology, Nashville VA Medical Center, Nashville, Tennessee 37232, USA
Annu Rev Physiol 64:803-43. 2002..cation-chloride cotransporters are positional candidates for Mendelian human disorders, and the K-Cl cotransporter KCC3, in particular, may be involved in degenerative peripheral neuropathies linked to chromosome 15q14...
- A dominant negative mutant of the KCC1 K-Cl cotransporter: both N- and C-terminal cytoplasmic domains are required for K-Cl cotransport activityS Casula
Molecular Medicine and Renal Units, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
J Biol Chem 276:41870-8. 2001..Delta(N)117 also exhibited dominant negative inhibition of human KCC1 and KCC3 and, with lower potency, mouse KCC4 and rat KCC2.
- Mutation analysis of the potassium chloride cotransporter KCC3 (SLC12A6) in rolandic and idiopathic generalized epilepsyO K Steinlein
Institute of Human Genetics, Rheinische Friedrich Wilhelms Universitat, D 53111, Bonn, Germany
Epilepsy Res 44:191-5. 2001..One of the most promising candidate genes is the brain-expressed potassium chloride cotransporter KCC3, given that this class of ion transporter has been implicated in the regulation of neuronal chloride activity...
- Localization of the K(+)-Cl(-) cotransporter, KCC3, in the central and peripheral nervous systems: expression in the choroid plexus, large neurons and white matter tractsM M Pearson
Department of Neurosurgery, Vanderbilt University Medical Center, Nashville, TN 37232, USA
Neuroscience 103:481-91. 2001..Northern blot confirmed the presence of two distinct forms of KCC3, KCC3a and KCC3b, generated by the inclusion of different first coding exons...
- Functional comparison of the K+-Cl- cotransporters KCC1 and KCC4A Mercado
Molecular Physiology Unit, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán and Instituto de Investigaciones Biomédicas, Universidad Nacional Autonoma de Mexico, Tlalpan 14000, Mexico City, Mexico
J Biol Chem 275:30326-34. 2000..cotransporter gene family and fall into two phylogenetic subgroups: KCC2 paired with KCC4 and KCC1 paired with KCC3. We report a functional comparison in Xenopus oocytes of KCC1 and KCC4, widely expressed representatives of these ..
- Cloning, characterization, and chromosomal location of a novel human K+-Cl- cotransporterK Hiki
Department of Human Immunology, Hanson Centre for Cancer Research, Institute of Medical and Veterinary Science and University of Adelaide, Adelaide, South Australia 5000
J Biol Chem 274:10661-7. 1999..We have referred to the predicted protein as K+-Cl- cotransporter 3 (KCC3)...
- Functional analysis of a potassium-chloride co-transporter 3 (SLC12A6) promoter polymorphism leading to an additional DNA methylation siteDirk Moser
Department of Neurobehavioral Genetics, Institute of Psychobiology, University of Trier, Trier, Germany
Neuropsychopharmacology 34:458-67. 2009The human potassium-chloride co-transporter 3 (KCC3, SLC12A6) is involved in cell proliferation and in electro-neutral movement of ions across the cell membrane...
- Molecular genetics of bipolar disorder and depressionTadafumi Kato
Laboratory for Molecular Dynamics of Mental Disorders, RIKEN Brain Science Institute, Wako, Saitama, Japan
Psychiatry Clin Neurosci 61:3-19. 2007..Finally, this report addresses some possible causes for the lack of replication in this field...
- Functional and molecular characterization of multiple K-Cl cotransporter isoforms in corneal epithelial cellsJosé E Capó-Aponte
Department of Biological Sciences, State University of New York, State College of Optometry, 33 West 42nd Street, New York, NY 10036, USA
Exp Eye Res 84:1090-103. 2007..RCEC, primary human CEC (pHCEC), and primary bovine CEC (BCEC) plasma membrane enriched fractions revealed KCC1, KCC3, and KCC4 isoform expression, whereas KCC2 was undetectable...
- Homooligomeric and heterooligomeric associations between K+-Cl- cotransporter isoforms and between K+-Cl- and Na+-K+-Cl- cotransportersCharles F Simard
Nephrology Research Group, L Hôtel Dieu de Québec Research Institution, Department of Medicine, Faculty of Medicine, Laval University, Quebec, Quebec G1R 2J6, Canada
J Biol Chem 282:18083-93. 2007..Through additional coimmunoprecipitation studies, we have also found that KCC1 and KCC3 had the potential of assembling into various types of CCC-CCC oligomers as well, although the interactions ..
- Disruption of erythroid K-Cl cotransporters alters erythrocyte volume and partially rescues erythrocyte dehydration in SAD miceMarco B Rust
Zentrum fur Molekulare Neurobiologie Hamburg, Universitat Hamburg, Hamburg, Germany
J Clin Invest 117:1708-17. 2007..To address the roles of individual K-Cl cotransporter isoforms in rbc volume homeostasis, we disrupted the Kcc1 and Kcc3 genes in mice...
- Characterization of glial cell K-Cl cotransportKenneth B E Gagnon
Cell Biophysics Group, Wright State University, Dayton, OH 4543, USA
Cell Physiol Biochem 20:121-30. 2007..The molecular mechanism of K-Cl cotransport (KCC) consists of at least 4 isoforms, KCC 1, 2, 3, and 4 which, in multiple combinations, exist in most cells, including erythrocytes and neuronal cells...
- Functional significance of channels and transporters expressed in the inner ear and kidneyFlorian Lang
Department of Physiology, Eberhard Karls University of Tubingen, Gmelinstrasse 5, Tubingen, Germany
Am J Physiol Cell Physiol 293:C1187-208. 2007..channels (KCNJ10, KCNQ1, KCNE1, and KCNMA1), Na(+)-2Cl(-)-K(+) cotransporter (SLC12A2), K(+)/Cl(-) cotransporters (KCC3 and KCC4), Cl(-) channels (BSND and CLCNKA + CLCNKB), and H(+)-ATPase (ATP6V1B1 and ATPV0A4) cause hearing loss...
- Distal truncation of KCC3 in non-French Canadian HMSN/ACC familiesA Salin-Cantegrel
Centre for the Study of Brain Diseases, CHUM Research Centre Notre Dame Hospital and the University of Montreal, Montreal, Quebec, Canada
Neurology 69:1350-5. 2007..Mutations in the potassium-chloride cotransporter 3 gene (KCC3) were identified as responsible for HMSN/ACC in the French Canadian (FC) population...
- WNK4 kinase is a negative regulator of K+-Cl- cotransportersTomas Garzon-Muvdi
Molecular Physiology Unit, Vasco de Quiroga No 15, Tlalpan 14000, Mexico City, Mexico
Am J Physiol Renal Physiol 292:F1197-207. 2007..of Xenopus laevis oocytes, here we show that WNK4 inhibits the activity of the K(+)-Cl(-) cotransporters KCC1, KCC3, and KCC4 under cell swelling, a condition in which these cotransporters are maximally active...
- K+-Cl- Cotransporter-3a Up-regulates Na+,K+-ATPase in Lipid Rafts of Gastric Luminal Parietal CellsTakuto Fujii
Department of Pharmaceutical Physiology, University of Toyama, Toyama 930 0194, Japan
J Biol Chem 283:6869-77. 2008..We found that KCC3a but not KCC3b mRNA was highly expressed, and KCC3a protein was predominantly expressed in the basolateral membrane ..
- Apparent intermediate K conductance channel hyposmotic activation in human lens epithelial cellsPeter K Lauf
Cell Biophysics Group, 054 Biological Sciences Bldg, Wright State Univ Boonshoft School of Medicine, Dayton, OH 45435, USA
Am J Physiol Cell Physiol 294:C820-32. 2008..RT-PCR and immunochemistry confirmed the presence of KCa3.1 channels, aside of the KCC1, KCC2, KCC3 and KCC4 isoforms...
- Chloride influx provokes lamellipodium formation in microglial cellsSusanna Zierler
Department of Cell Biology, Paris Lodron University of Salzburg, Salzburg, Austria
Cell Physiol Biochem 21:55-62. 2008..in BV-2 cells included, swelling-activated chloride channels as well as the KCl cotransporters, KCC1, KCC2, KCC3, and KCC4...
- K-Cl cotransport in red blood cells from patients with KCC3 isoform mutantsP K Lauf
Cell Biophysics Group, Department of Pathology, Wright State University, Boonshoft School of Medicine, 3640 Col Glenn Hwy, Dayton, OH 45435, USA
Biochem Cell Biol 84:1034-44. 2006..of 8 patients with hereditary motor and sensory neuropathy with agenesis of corpus callosum (HMSN-ACC) with defined KCC3 mutations (813FsX813 and Phe529FsX532) involving the truncations of 338 and 619 C-terminal amino acids, ..
- HMSN/ACC truncation mutations disrupt brain-type creatine kinase-dependant activation of K+/Cl- co-transporter 3Adèle Salin-Cantegrel
Department of Medicine, Centre of Excellence in Neuromics, CHUM Research Centre, University of Montreal, Montreal, QC, Canada
Hum Mol Genet 17:2703-11. 2008The potassium-chloride co-transporter 3 (KCC3) is mutated in hereditary motor and sensory neuropathy with agenesis of the corpus callosum (HMSN/ACC); however, the molecular mechanisms of HMSN/ACC pathogenesis and the exact role of KCC3 in ..
- Roles of the cation-chloride cotransporters in neurological diseaseKristopher T Kahle
Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
Nat Clin Pract Neurol 4:490-503. 2008..the Na-K-2Cl cotransporter NKCC1, which mediates chloride influx, and various K-Cl cotransporters--such as KCC2 and KCC3-that extrude chloride...
- Functional association between K+-Cl- cotransporter-4 and H+,K+-ATPase in the apical canalicular membrane of gastric parietal cellsTakuto Fujii
Department of Pharmaceutical Physiology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan
J Biol Chem 284:619-29. 2009..In contrast, KCC1, KCC2, and KCC3 were not found in either SAV or tubulovesicles. KCC4 coimmunoprecipitated with H+,K+-ATPase in the lysate of SAV...
- Molecular physiology of cation-coupled Cl- cotransport: the SLC12 familySteven C Hebert
Department of Cellular and Molecular Physiology, Yale University Medical School, 333 Cedar Street, P O Box 208026, SHM B147, New Haven, CT 06520 8026, USA
Pflugers Arch 447:580-93. 2004..In addition, knockout mice for many members of this family have generated important new information regarding their respective physiological roles...
- Cell-type specific distribution of chloride transporters in the rat suprachiasmatic nucleusM A Belenky
Department of Cell and Developmental Biology, Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem, Israel
Neuroscience 165:1519-37. 2010..Here we report that the K(+)/Cl(-) cotransporter isoforms KCC4 and KCC3 are expressed solely in vasopressin (VP) neurons in the rat SCN whereas KCC1 is expressed in VIP neurons, similar ..
- Andermann syndrome can be a phenocopy of hereditary motor and sensory neuropathy--report of a discordant sibship with a compound heterozygous mutation of the KCC3 geneS Rudnik-Schoneborn
Institute of Human Genetics, RWTH Aachen University, Aachen, Germany
Neuropediatrics 40:129-33. 2009..Mutation analysis of the KCC3 (SLC12A6) gene showed a compound heterozygous mutation; a maternal missense mutation c.1616G>A (p...
- Mutations affecting GABAergic signaling in seizures and epilepsyAristea S Galanopoulou
Saul R Korey Department of Neurology and Dominick P Purpura Department of Neuroscience, Albert Einstein College of Medicine, 1410 Pelham Parkway South, Kennedy Center Room 306, Bronx, NY 10461, USA
Pflugers Arch 460:505-23. 2010..These include the chloride channel 2 (CLCN2) and the potassium chloride cotransporter KCC3. The pathogenic role of CLCN2 mutations has not been clearly demonstrated and may represent either susceptibility ..
- Novel SPG11 mutations in Asian kindreds and disruption of spatacsin function in the zebrafishLaura Southgate
Department of Medical and Molecular Genetics, King s College London, School of Medicine, Floor 8 Tower Wing, Guy s Hospital, London, SE1 9RT, UK
Neurogenetics 11:379-89. 2010..Homozygosity mapping and direct sequencing were used to assess the ACCPN, SPG11, and SPG21 loci in four inbred kindreds originating from the Indian subcontinent...
- Deficiency of electroneutral K+-Cl- cotransporter 3 causes a disruption in impulse propagation along peripheral nervesYuan Ting Sun
Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan
Glia 58:1544-52. 2010..Mutation in SLC12A6 gene encoding KCC3 results in an autosomal recessive disease, known as agenesis of the corpus callosum associated with peripheral ..
- The NH(2)-terminus of K(+)-Cl(-) cotransporter 3a is essential for up-regulation of Na(+),K(+)-ATPase activityTakuto Fujii
Department of Pharmaceutical Physiology, University of Toyama, Toyama 930 0194, Japan
Biochem Biophys Res Commun 399:683-7. 2010K(+)-Cl(-) cotransporter-3 has two major amino terminal variants, KCC3a and KCC3b. In LLC-PK1 cells, exogenously expressed KCC3a co-immunoprecipitated with endogenous Na(+),K(+)-ATPase alpha1-subunit (alpha1NaK), accompanying significant ..
- Cellular expression of the K+-Cl- cotransporter KCC3 in the central nervous system of mouseMasoud Shekarabi
Centre of Excellence in Neuromics, CHUM Research Center and Department of Medicine, University of Montreal, Notre Dame Hospital, 1560 Sherbrooke East, De Seve Pavillion, room Y 3616 2, Montreal, QC, H2L 4M1, Canada
Brain Res 1374:15-26. 2011..Two major splice variants, KCC3a and KCC3b, were shown to be expressed in adult mouse tissues...
- Role of KCC3 in Schwann cell developmentNellie Byun; Fiscal Year: 2005..with mutations in the human KCC3 gene who suffer from a neurological disorder termed Andermann syndrome, or ACCPN. Both show myelination abnormalities in peripheral nerves, e.g...
- Novel Mouse Models for the Peripheral Neuropathy Disorder ACCPNEric J Delpire; Fiscal Year: 2010..3 (KCC3) are responsible for one of the most severe, early onset peripheral neuropathy disorders called ACCPN or "Agenesis of Corpus Callosum associated with Peripheral Neuropathy"...
- Molecular Physiology of Renal K-Cl CotransportersDavid Mount; Fiscal Year: 2007..tubule, isotonic swelling induced by apical Na absorption activates basolateral K+ -Cl- cotransport mediated by KCC3 and KCC4, implicating these transporters in proximal re-absorption of filtered Na+-Cl- and other solutes...
- Third Symposium Cell Volume & Signalling RegulationPETER LAUF; Fiscal Year: 2003..This meeting's success on U.S. soil will foster continuation of gathering of high-caliber scientists at subsequent international meetings ..
- Proteomics of M-L antigens modulating cation transportPETER LAUF; Fiscal Year: 2004....
- REGULATION OF THE NA+ COUPLED CL- COTRANSPORTERSSteven Hebert; Fiscal Year: 2004..This has important relevance to understanding salt and water handling by the kidney in health and disease. ..