KCC3

Summary

Gene Symbol: KCC3
Description: solute carrier family 12 (potassium/chloride transporter), member 6
Alias: ACCPN, KCC3, KCC3A, KCC3B, 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 transporters), member 6, solute carrier family 12 member 6
Species: human

Top Publications

  1. ncbi Molecular cloning and functional characterization of KCC3, a new K-Cl cotransporter
    J 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. 1999
  2. ncbi NH2-terminal heterogeneity in the KCC3 K+-Cl- cotransporter
    Adriana Mercado
    Renal Division, Brigham and Women s Hospital, Boston, MA 02115, USA
    Am J Physiol Renal Physiol 289:F1246-61. 2005
  3. pmc Axonal and periaxonal swelling precede peripheral neurodegeneration in KCC3 knockout mice
    Nellie 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
  4. pmc A deletion mutation in Slc12a6 is associated with neuromuscular disease in gaxp mice
    Yan Jiao
    Department of Orthopaedic Surgery Campbell Clinic, University of Tennessee Health Science Center, Memphis, TN 38163, USA
    Genomics 91:407-14. 2008
  5. ncbi Insulin-like growth factor 1 stimulates KCl cotransport, which is necessary for invasion and proliferation of cervical cancer and ovarian cancer cells
    Meng Ru Shen
    Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan
    J Biol Chem 279:40017-25. 2004
  6. ncbi 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
  7. ncbi IGF-1 upregulates electroneutral K-Cl cotransporter KCC3 and KCC4 which are differentially required for breast cancer cell proliferation and invasiveness
    Yueh Mei Hsu
    Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan
    J Cell Physiol 210:626-36. 2007
  8. ncbi KCC isoforms in a human lens epithelial cell line (B3) and lens tissue extracts
    Sandeep 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
  9. ncbi Differential expression pattern of chloride transporters NCC, NKCC2, KCC1, KCC3, KCC4, and AE3 in the developing rat auditory brainstem
    Michael Becker
    Abteilung Tierphysiologie, Universitat Kaiserslautern, Kaiserslautern, Germany
    Cell Tissue Res 312:155-65. 2003
  10. ncbi Aberrant chloride transport contributes to anoxic/ischemic white matter injury
    Sameh A Malek
    Ottawa Health Research Institute, Ottawa Hospital, University of Ottawa, Canada K1Y 4K9
    J Neurosci 23:3826-36. 2003

Scientific Experts

Detail Information

Publications83

  1. ncbi Molecular cloning and functional characterization of KCC3, a new K-Cl cotransporter
    J 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. 1999
    We isolated and characterized a novel K-Cl cotransporter, KCC3, from human placenta. The deduced protein contains 1,150 amino acids...
  2. ncbi NH2-terminal heterogeneity in the KCC3 K+-Cl- cotransporter
    Adriana 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...
  3. pmc Axonal and periaxonal swelling precede peripheral neurodegeneration in KCC3 knockout mice
    Nellie 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...
  4. pmc A deletion mutation in Slc12a6 is associated with neuromuscular disease in gaxp mice
    Yan 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...
  5. ncbi Insulin-like growth factor 1 stimulates KCl cotransport, which is necessary for invasion and proliferation of cervical cancer and ovarian cancer cells
    Meng 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...
  6. ncbi 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...
  7. ncbi IGF-1 upregulates electroneutral K-Cl cotransporter KCC3 and KCC4 which are differentially required for breast cancer cell proliferation and invasiveness
    Yueh 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...
  8. ncbi KCC isoforms in a human lens epithelial cell line (B3) and lens tissue extracts
    Sandeep 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...
  9. ncbi Differential expression pattern of chloride transporters NCC, NKCC2, KCC1, KCC3, KCC4, and AE3 in the developing rat auditory brainstem
    Michael 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...
  10. ncbi Aberrant chloride transport contributes to anoxic/ischemic white matter injury
    Sameh 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...
  11. pmc Molecular evidence for a role for K+-Cl- cotransporters in the kidney
    Zesergio Melo
    Molecular Physiology Unit, Vasco de Quiroga No 15, Tlalpan 14000, Mexico City, Mexico
    Am J Physiol Renal Physiol 305:F1402-11. 2013
    K(+)-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..
  12. ncbi Hereditary motor and sensory neuropathy with agenesis of the corpus callosum
    Nicolas 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 ..
  13. ncbi Electroneutral cation-chloride cotransporters in the central nervous system
    Adriana 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 ..
  14. doi Similar effects of all WNK3 variants on SLC12 cotransporters
    Silvia 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...
  15. pmc Relative contribution of chloride channels and transporters to regulatory volume decrease in human glioma cells
    Nola 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.
  16. ncbi The role of potassium chloride cotransporters in murine and human sperm volume regulation
    T 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...
  17. doi Expanding the differential diagnosis of inherited neuropathies with non-uniform conduction: Andermann syndrome
    Charles 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 ..
  18. ncbi Basolateral Cl- transport is stimulated by terbutaline in adult rat alveolar epithelial cells
    S 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...
  19. pmc N-terminal serine dephosphorylation is required for KCC3 cotransporter full activation by cell swelling
    Zesergio 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...
  20. pmc A trafficking-deficient mutant of KCC3 reveals dominant-negative effects on K-Cl cotransport function
    Jinlong 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 ..
  21. pmc N-ethylmaleimide activates a Cl(-)-independent component of K(+) flux in mouse erythrocytes
    Boris 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...
  22. doi Cation-chloride cotransporters in the nervous system: General features and clinical correlations
    Eduardo 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...
  23. doi K(+)-Cl(-) cotransporter 1 (KCC1) negatively regulates NGF-induced neurite outgrowth in PC12 cells
    Hikaru 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...
  24. doi High-grade glioma motility reduced by genetic knockdown of KCC3
    Kenneth 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 ..
  25. pmc Potassium-chloride cotransporter 3 interacts with Vav2 to synchronize the cell volume decrease response with cell protrusion dynamics
    Adèle Salin-Cantegrel
    Centre of Excellence in Neuroscience of University of Montreal, Montreal, Quebec, Canada
    PLoS ONE 8:e65294. 2013
    Loss-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 ..
  26. doi Role of cholesterol in functional association between K(+)-Cl(-) cotransporter-3a and Na+,K(+)-ATPase
    Kyosuke Fujita
    Department of Pharmaceutical Physiology, University of Toyama, Toyama 930 0194, Japan
    Biochem Biophys Res Commun 424:136-40. 2012
    K(+)-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...
  27. pmc Raising cytosolic Cl- in cerebellar granule cells affects their excitability and vestibulo-ocular learning
    Patricia 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...
  28. ncbi Patterns of cation-chloride cotransporter expression during embryonic rodent CNS development
    Hong 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...
  29. doi Apparent intermediate K conductance channel hyposmotic activation in human lens epithelial cells
    Peter 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...
  30. doi Deficiency of electroneutral K+-Cl- cotransporter 3 causes a disruption in impulse propagation along peripheral nerves
    Yuan 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 ..
  31. doi 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 gene
    S 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...
  32. pmc Cell-type specific distribution of chloride transporters in the rat suprachiasmatic nucleus
    M 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 ..
  33. pmc Sites of regulated phosphorylation that control K-Cl cotransporter activity
    Jesse 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 ..
  34. doi Functional association between K+-Cl- cotransporter-4 and H+,K+-ATPase in the apical canalicular membrane of gastric parietal cells
    Takuto 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...
  35. doi Roles of the cation-chloride cotransporters in neurological disease
    Kristopher 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...
  36. doi HMSN/ACC truncation mutations disrupt brain-type creatine kinase-dependant activation of K+/Cl- co-transporter 3
    Adèle 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. 2008
    The 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 ..
  37. doi Functional analysis of a potassium-chloride co-transporter 3 (SLC12A6) promoter polymorphism leading to an additional DNA methylation site
    Dirk Moser
    Department of Neurobehavioral Genetics, Institute of Psychobiology, University of Trier, Trier, Germany
    Neuropsychopharmacology 34:458-67. 2009
    The human potassium-chloride co-transporter 3 (KCC3, SLC12A6) is involved in cell proliferation and in electro-neutral movement of ions across the cell membrane...
  38. doi Chloride influx provokes lamellipodium formation in microglial cells
    Susanna 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...
  39. ncbi Cloning, characterization, and chromosomal location of a novel human K+-Cl- cotransporter
    K 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)...
  40. pmc K-Cl cotransporter gene expression during human and murine erythroid differentiation
    Dao 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
    ..Message levels for KCC1 and KCC3b were low. The ratios of KCC RNA levels varied among individuals but were similar in sickle and normal RBC...
  41. pmc Transit defect of potassium-chloride Co-transporter 3 is a major pathogenic mechanism in hereditary motor and sensory neuropathy with agenesis of the corpus callosum
    Adèle 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. 2011
    Missense 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 ..
  42. pmc Volume regulation and KCl cotransport in reticulocyte populations of sickle and normal red blood cells
    Maa 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)...
  43. pmc Knocking down of the KCC2 in rat hippocampal neurons increases intracellular chloride concentration and compromises neuronal survival
    Christophe 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...
  44. doi Genetic factors underlying the risk of thalidomide-related neuropathy in patients with multiple myeloma
    David 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)...
  45. doi Cellular expression of the K+-Cl- cotransporter KCC3 in the central nervous system of mouse
    Masoud 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...
  46. doi The NH(2)-terminus of K(+)-Cl(-) cotransporter 3a is essential for up-regulation of Na(+),K(+)-ATPase activity
    Takuto Fujii
    Department of Pharmaceutical Physiology, University of Toyama, Toyama 930 0194, Japan
    Biochem Biophys Res Commun 399:683-7. 2010
    K(+)-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 ..
  47. ncbi Function of K⁺-Cl⁻ cotransporters in the acid secretory mechanism of gastric parietal cells
    Takuto 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...
  48. pmc Novel SPG11 mutations in Asian kindreds and disruption of spatacsin function in the zebrafish
    Laura 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...
  49. pmc Mutations affecting GABAergic signaling in seizures and epilepsy
    Aristea 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 ..
  50. doi K+-Cl- Cotransporter-3a Up-regulates Na+,K+-ATPase in Lipid Rafts of Gastric Luminal Parietal Cells
    Takuto 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 of rat ..
  51. ncbi KCl cotransporter-3 down-regulates E-cadherin/beta-catenin complex to promote epithelial-mesenchymal transition
    Yueh 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...
  52. ncbi Regulation of K-Cl cotransport: from function to genes
    N 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...
  53. ncbi Expression of K+-Cl- cotransporters in the alpha-cells of rat endocrine pancreas
    Sarah 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. 2004
    The 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...
  54. pmc Loss of K-Cl co-transporter KCC3 causes deafness, neurodegeneration and reduced seizure threshold
    Thomas 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...
  55. ncbi 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...
  56. ncbi Molecular physiology of cation-coupled Cl- cotransport: the SLC12 family
    Steven 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...
  57. ncbi Ammonium transport and pH regulation by K(+)-Cl(-) cotransporters
    Marc 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...
  58. ncbi Influence of K-Cl cotransporter activity on activation of volume-sensitive Cl- channels in human osteoblasts
    Margot Bräuer
    Department of Applied Physiology, University of Ulm, 89081 Ulm, Germany
    Am J Physiol Cell Physiol 285:C22-30. 2003
    ....
  59. ncbi The K-Cl cotransporter KCC3 is mutant in a severe peripheral neuropathy associated with agenesis of the corpus callosum
    Heidi 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. 2002
    Peripheral 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...
  60. ncbi K-Cl co-transport: immunocytochemical and functional evidence for more than one KCC isoform in high K and low K sheep erythrocytes
    P 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)...
  61. ncbi Human and murine phenotypes associated with defects in cation-chloride cotransport
    Eric 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...
  62. ncbi A dominant negative mutant of the KCC1 K-Cl cotransporter: both N- and C-terminal cytoplasmic domains are required for K-Cl cotransport activity
    S 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.
  63. ncbi Mutation analysis of the potassium chloride cotransporter KCC3 (SLC12A6) in rolandic and idiopathic generalized epilepsy
    O 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...
  64. ncbi Localization of the K(+)-Cl(-) cotransporter, KCC3, in the central and peripheral nervous systems: expression in the choroid plexus, large neurons and white matter tracts
    M 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...
  65. ncbi Functional comparison of the K+-Cl- cotransporters KCC1 and KCC4
    A 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 ..
  66. ncbi Chloride transport in the kidney: lessons from human disease and knockout mice
    Thomas 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.
  67. ncbi Rare variants of the gene encoding the potassium chloride co-transporter 3 are associated with bipolar disorder
    Jobst 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)...
  68. ncbi Distal truncation of KCC3 in non-French Canadian HMSN/ACC families
    A 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...
  69. ncbi Functional significance of channels and transporters expressed in the inner ear and kidney
    Florian 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...
  70. ncbi Characterization of glial cell K-Cl cotransport
    Kenneth 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...
  71. pmc Disruption of erythroid K-Cl cotransporters alters erythrocyte volume and partially rescues erythrocyte dehydration in SAD mice
    Marco 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...
  72. ncbi Homooligomeric and heterooligomeric associations between K+-Cl- cotransporter isoforms and between K+-Cl- and Na+-K+-Cl- cotransporters
    Charles 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 ..
  73. pmc Functional and molecular characterization of multiple K-Cl cotransporter isoforms in corneal epithelial cells
    José 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...
  74. ncbi Molecular genetics of bipolar disorder and depression
    Tadafumi 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...
  75. ncbi K-Cl cotransport in red blood cells from patients with KCC3 isoform mutants
    P 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, ..
  76. ncbi WNK4 kinase is a negative regulator of K+-Cl- cotransporters
    Tomas 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...
  77. ncbi KCC3 and KCC4 expression in rat adult forebrain
    P 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 ..
  78. ncbi Hereditary spastic paraplegia with thin corpus callosum: reduction of the SPG11 interval and evidence for further genetic heterogeneity
    Alexander 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)...
  79. ncbi Novel truncating and missense mutations of the KCC3 gene associated with Andermann syndrome
    G 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.
  80. ncbi Neurogenic mechanisms contribute to hypertension in mice with disruption of the K-Cl cotransporter KCC3
    Marco B Rust
    Zentrum fur Molekulare Neurobiologie Hamburg, Universitat Hamburg, Universitatsklinikum Hamburg Eppendorf, Hamburg, Germany
    Circ Res 98:549-56. 2006
    The 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 ..
  81. ncbi Thin corpus callosum and amyotrophy in spastic paraplegia--case report and review of literature
    Beate 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...
  82. ncbi Cloning and characterization of KCC3 and KCC4, new members of the cation-chloride cotransporter gene family
    D 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...

Research Grants28

  1. Role of KCC3 in Schwann cell development
    Nellie 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...
  2. Molecular Physiology of Renal K-Cl Cotransporters
    David 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...
  3. MOLECULAR PHYSIOLOGY OF RENAL K+/ CL- COTRANSPORTERS
    David Mount; Fiscal Year: 2003
    ..Subsequently the principal investigator has cloned two completely new co-transporters KCC3 and KCC4...
  4. Proteomics of M-L antigens modulating cation transport
    PETER LAUF; Fiscal Year: 2004
    ....
  5. Third Symposium Cell Volume & Signalling Regulation
    PETER 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 ..
  6. STRUCTURE AND FUNCTION OF ROMK CHANNEL IN KIDNEY
    Steven Hebert; Fiscal Year: 2004
    ..g., mechanism for continued renal K+ loss and role of prostaglandin E2 in renal NaC1 and K+ wasting) and may best be addressed using an animal model. ..
  7. Cellular and Molecular Physiology of Organ Function
    EMILE BOULPAEP; Fiscal Year: 2007
    ....
  8. STRUCTURE AND FUNCTION OF ROMK CHANNEL IN KIDNEY
    Steven Hebert; Fiscal Year: 2007
    ..These mice will also provide a resource for others interested in ROMK function in non- renal cells (Gl tract, brain, etc). ..
  9. REGULATION OF THE NA+ COUPLED CL- COTRANSPORTERS
    Steven Hebert; Fiscal Year: 2004
    ..This has important relevance to understanding salt and water handling by the kidney in health and disease. ..