Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2019

Open Access 01-12-2019 | Sickle Cell Anemia | Review

K+-Cl− cotransporter 1 (KCC1): a housekeeping membrane protein that plays key supplemental roles in hematopoietic and cancer cells

Authors: A. P. Garneau, S. Slimani, L. E. Tremblay, M. J. Fiola, A. A. Marcoux, P. Isenring

Published in: Journal of Hematology & Oncology | Issue 1/2019

Login to get access

Abstract

During the 1970s, a Na+-independent, ouabain-insensitive, N-ethylmaleimide-stimulated K+-Cl− cotransport mechanism was identified in red blood cells for the first time and in a variety of cell types afterward. During and just after the mid-1990s, three closely related isoforms were shown to account for this mechanism. They were termed K+-Cl− cotransporter 1 (KCC1), KCC3, and KCC4 according to the nomenclature of Gillen et al. (1996) who had been the first research group to uncover the molecular identity of a KCC, that is, of KCC1 in rabbit kidney. Since then, KCC1 has been found to be the most widely distributed KCC isoform and considered to act as a housekeeping membrane protein. It has perhaps received less attention than the other isoforms for this reason, but as will be discussed in the following review, there is probably more to KCC1 than meets the eye. In particular, the so-called housekeeping gene also appears to play crucial and specific roles in normal as well as pathological hematopoietic and in cancer cells.
Footnotes
1
Sequences used to generate the phylogram of Fig. 1b:
  • CCC Accession numbers
  • NKCC1 NP_001037.1
  • NKCC2 NP_000329.2
  • NCC NP_000330.2
  • KCC1 NP_005063.1
  • KCC2 NP_001128243.1
  • KCC3 NP_598408.1
  • KCC4 NP_006589.2
  • CCC8 NP_064631.2
  • CCC9 NP_078904.3
 
Literature
1.
2.
Xu JC, Lytle C, Zhu TT, Payne JA, Benz E Jr, Forbush B 3rd. Molecular cloning and functional expression of the bumetanide-sensitive Na-K-Cl cotransporter. Proc Natl Acad Sci U S A. 1994;91(6):2201–5.PubMedPubMedCentralCrossRef
3.
Garneau AP, Marcoux AA, Frenette-Cotton R, Mac-Way F, Lavoie JL, Isenring P. Molecular insights into the normal operation, regulation, and multisystemic roles of K(+)-Cl(-) cotransporter 3 (KCC3). Am J Physiol Cell Physiol. 2017;313(5):C516–C32.PubMedCrossRef
4.
Marcoux AA, Garneau AP, Frenette-Cotton R, Slimani S, Mac-Way F, Isenring P. Molecular features and physiological roles of K(+)-Cl(-) cotransporter 4 (KCC4). Biochim Biophys Acta Gen Subj. 2017;1861(12):3154–66.PubMedCrossRef
5.
Lauf PK, Theg BE. A chloride dependent K+ flux induced by N-ethylmaleimide in genetically low K+ sheep and goat erythrocytes. Biochem Biophys Res Commun. 1980;92(4):1422–8.PubMedCrossRef
6.
7.
Kregenow FM. The response of duck erythrocytes to nonhemolytic hypotonic media. Evidence for a volume-controlling mechanism. J Gen Physiol. 1971;58(4):372–95.PubMedPubMedCentralCrossRef
8.
Hubner CA, Stein V, Hermans-Borgmeyer I, Meyer T, Ballanyi K, Jentsch TJ. Disruption of KCC2 reveals an essential role of K-Cl cotransport already in early synaptic inhibition. Neuron. 2001;30(2):515–24.PubMedCrossRef
9.
Casaubon LK, Melanson M, Lopes-Cendes I, Marineau C, Andermann E, Andermann F, et al. The gene responsible for a severe form of peripheral neuropathy and agenesis of the corpus callosum maps to chromosome 15q. Am J Hum Genet. 1996;58(1):28–34.PubMedPubMedCentral
10.
Kahle KT, Merner ND, Friedel P, Silayeva L, Liang B, Khanna A, et al. Genetically encoded impairment of neuronal KCC2 cotransporter function in human idiopathic generalized epilepsy. EMBO Rep. 2014;15(7):766–74.PubMedPubMedCentralCrossRef
11.
Gillen CM, Brill S, Payne JA, Forbush B 3rd. Molecular cloning and functional expression of the K-Cl cotransporter from rabbit, rat, and human. A new member of the cation-chloride cotransporter family. J Biol Chem. 1996;271(27):16237–44.PubMedCrossRef
12.
Su W, Shmukler BE, Chernova MN, Stuart-Tilley AK, de Franceschi L, Brugnara C, et al. Mouse K-Cl cotransporter KCC1: cloning, mapping, pathological expression, and functional regulation. Am J Physiol. 1999;277(5):C899–912.PubMedCrossRef
13.
Cell Physiology Source Book - Essentials of Membrane Biophysics. 4th ed: Elsevier; 2011. 248 p.
14.
Brown FC, Conway AJ, Cerruti L, Collinge JE, McLean C, Wiley JS, et al. Activation of the erythroid K-Cl cotransporter Kcc1 enhances sickle cell disease pathology in a humanized mouse model. Blood. 2015;126(26):2863–70.PubMedCrossRef
15.
Rust MB, Alper SL, Rudhard Y, Shmukler BE, Vicente R, Brugnara C, et al. Disruption of erythroid K-Cl cotransporters alters erythrocyte volume and partially rescues erythrocyte dehydration in SAD mice. J Clin Invest. 2007;117(6):1708–17.PubMedPubMedCentralCrossRef
16.
Zhang S, Wu X, Jiang T, Lu Y, Ma L, Liang M, et al. The up-regulation of KCC1 gene expression in cervical cancer cells by IGF-II through the ERK1/2MAPK and PI3K/AKT pathways and its significance. Eur J Gynaecol Oncol. 2009;30(1):29–34.PubMed
17.
Kajiya H, Okamoto F, Ohgi K, Nakao A, Fukushima H, Okabe K. Characteristics of ClC7 Cl- channels and their inhibition in mutant (G215R) associated with autosomal dominant osteopetrosis type II in native osteoclasts and hClcn7 gene-expressing cells. Pflugers Arch. 2009;458(6):1049–59.PubMedCrossRef
18.
Kajiya H, Okamoto F, Li JP, Nakao A, Okabe K. Expression of mouse osteoclast K-Cl Co-transporter-1 and its role during bone resorption. J Bone Miner Res. 2006;21(7):984–92.PubMedCrossRef
19.
Aull F. Potassium chloride cotransport in steady-state ascites tumor cells. Does bumetanide inhibit? Biochim Biophys Acta. 1981;643(2):339–45.PubMedCrossRef
20.
Perry PB, O'Neill WC. Swelling-activated K fluxes in vascular endothelial cells: volume regulation via K-Cl cotransport and K channels. Am J Physiol. 1993;265(3 Pt 1):C763–9.PubMedCrossRef
21.
Larson M, Spring KR. Volume regulation by Necturus gallbladder: basolateral KCl exit. J Membr Biol. 1984;81(3):219–32.PubMedCrossRef
22.
Anagnostopoulos T, Edelman A, Planelles G, Teulon J, Thomas SR. Transport of chlorine in the proximal tubule. Its effects on water-electrolyte absorption. J Physiol (Paris). 1984;79(3):132–8.
23.
Garay RP, Nazaret C, Hannaert PA, Cragoe EJ Jr. Demonstration of a [K+,Cl-]-cotransport system in human red cells by its sensitivity to [(dihydroindenyl)oxy]alkanoic acids: regulation of cell swelling and distinction from the bumetanide-sensitive [Na+,K+,Cl-]-cotransport system. Mol Pharmacol. 1988;33(6):696–701.PubMed
24.
Gusev GP, Agalakova NI, Lapin AV. Kinetics of K-Cl cotransport in frog erythrocyte membrane: effect of external sodium. J Membr Biol. 1999;172(3):203–13.PubMedCrossRef
25.
Sachs JR, Martin DW. The role of ATP in swelling-stimulated K-Cl cotransport in human red cell ghosts. Phosphorylation-dephosphorylation events are not in the signal transduction pathway. J Gen Physiol. 1993;102(3):551–73.PubMedCrossRef
26.
Kelley SJ, Dunham PB. Mechanism of swelling activation of K-Cl cotransport in inside-out vesicles of LK sheep erythrocyte membranes. Am J Physiol. 1996;270(4 Pt 1):C1122–30.PubMedCrossRef
27.
Jennings ML. al-Rohil N. Kinetics of activation and inactivation of swelling-stimulated K+/Cl- transport. The volume-sensitive parameter is the rate constant for inactivation. J Gen Physiol. 1990;95(6):1021–40.PubMedCrossRef
28.
Jennings ML, Schulz RK. Okadaic acid inhibition of KCl cotransport. Evidence that protein dephosphorylation is necessary for activation of transport by either cell swelling or N-ethylmaleimide. J Gen Physiol. 1991;97(4):799–817.PubMedCrossRef
29.
Payne JA, Stevenson TJ, Donaldson LF. Molecular characterization of a putative K-Cl cotransporter in rat brain. A neuronal-specific isoform. J Biol Chem. 1996;271(27):16245–52.PubMedCrossRef
30.
Hiki K, D'Andrea RJ, Furze J, Crawford J, Woollatt E, Sutherland GR, et al. Cloning, characterization, and chromosomal location of a novel human K+-Cl- cotransporter. J Biol Chem. 1999;274(15):10661–7.PubMedCrossRef
31.
Mount DB, Mercado A, Song L, Xu J, George AL Jr, Delpire E, et al. Cloning and characterization of KCC3 and KCC4, new members of the cation-chloride cotransporter gene family. J Biol Chem. 1999;274(23):16355–62.PubMedCrossRef
32.
Race JE, Makhlouf FN, Logue PJ, Wilson FH, Dunham PB, Holtzman EJ. Molecular cloning and functional characterization of KCC3, a new K-Cl cotransporter. Am J Physiol. 1999;277(6 Pt 1):C1210–9.PubMedCrossRef
33.
Payne JA, Xu JC, Haas M, Lytle CY, Ward D, Forbush B 3rd. Primary structure, functional expression, and chromosomal localization of the bumetanide-sensitive Na-K-Cl cotransporter in human colon. J Biol Chem. 1995;270(30):17977–85.PubMedCrossRef
34.
Igarashi P, Vanden Heuvel GB, Payne JA, Forbush B 3rd. Cloning, embryonic expression, and alternative splicing of a murine kidney-specific Na-K-Cl cotransporter. Am J Physiol. 1995;269(3 Pt 2):F405–18.PubMed
35.
Delpire E, Rauchman MI, Beier DR, Hebert SC, Gullans SR. Molecular cloning and chromosome localization of a putative basolateral Na(+)-K(+)-2Cl- cotransporter from mouse inner medullary collecting duct (mIMCD-3) cells. J Biol Chem. 1994;269(41):25677–83.PubMed
36.
37.
Dereeper A, Guignon V, Blanc G, Audic S, Buffet S, Chevenet F, et al. Phylogeny.fr: robust phylogenetic analysis for the non-specialist. Nucleic Acids Res. 2008;36(Web Server issue):W465-W469.PubMedPubMedCentralCrossRef
38.
Crable SC, Hammond SM, Papes R, Rettig RK, Zhou GP, Gallagher PG, et al. Multiple isoforms of the KC1 cotransporter are expressed in sickle and normal erythroid cells. Exp Hematol. 2005;33(6):624–31.PubMedCrossRef
39.
Pan D, Kalfa TA, Wang D, Risinger M, Crable S, Ottlinger A, et al. K-Cl cotransporter gene expression during human and murine erythroid differentiation. J Biol Chem. 2011;286(35):30492–503.PubMedPubMedCentralCrossRef
40.
Lauf PK, Zhang J, Delpire E, Fyffe RE, Mount DB, Adragna NC. K-Cl co-transport: immunocytochemical and functional evidence for more than one KCC isoform in high K and low K sheep erythrocytes. Comp Biochem Physiol A Mol Integr Physiol. 2001;130(3):499–509.PubMedCrossRef
41.
Jennings ML, Adame MF. Direct estimate of 1:1 stoichiometry of K(+)-Cl(-) cotransport in rabbit erythrocytes. Am J Physiol Cell Physiol. 2001;281(3):C825–32.PubMedCrossRef
42.
Mercado A, Song L, Vazquez N, Mount DB, Gamba G. Functional comparison of the K+-Cl- cotransporters KCC1 and KCC4. J Biol Chem. 2000;275(39):30326–34.PubMedCrossRef
43.
Bergeron MJ, Gagnon E, Wallendorff B, Lapointe JY, Isenring P. Ammonium transport and pH regulation by K(+)-Cl(-) cotransporters. Am J Physiol Renal Physiol. 2003;285(1):F68–78.PubMedCrossRef
44.
Simard CF, Bergeron MJ, Frenette-Cotton R, Carpentier GA, Pelchat ME, Caron L, et al. Homooligomeric and heterooligomeric associations between K+-Cl- cotransporter isoforms and between K+-Cl- and Na+-K+-Cl- cotransporters. J Biol Chem. 2007;282(25):18083–93.PubMedCrossRef
45.
46.
Rinehart J, Maksimova YD, Tanis JE, Stone KL, Hodson CA, Zhang J, et al. Sites of regulated phosphorylation that control K-Cl cotransporter activity. Cell. 2009;138(3):525–36.PubMedPubMedCentralCrossRef
47.
Frenette-Cotton R, Marcoux AA, Garneau AP, Noel M, Isenring P. Phosphoregulation of K(+) -Cl(-) cotransporters during cell swelling: novel insights. J Cell Physiol. 2018;233(1):396–408.PubMedCrossRef
48.
Armsby CC, Stuart-Tilley AK, Alper SL, Brugnara C. Resistance to osmotic lysis in BXD-31 mouse erythrocytes: association with upregulated K-Cl cotransport. Am J Physiol. 1996;270(3 Pt 1):C866–77.PubMedCrossRef
49.
Pellegrino CM, Rybicki AC, Musto S, Nagel RL, Schwartz RS. Molecular identification and expression of erythroid K:Cl cotransporter in human and mouse erythroleukemic cells. Blood Cells Mol Dis. 1998;24(1):31–40.PubMedCrossRef
50.
Canessa M, Romero JR, Lawrence C, Nagel RL, Fabry ME. Rate of activation and deactivation of K:Cl cotransport by changes in cell volume in hemoglobin SS, CC and AA red cells. J Membr Biol. 1994;142(3):349–62.PubMedCrossRef
51.
Parshina EY, Yusipovich AI, Platonova AA, Grygorczyk R, Maksimov GV, Orlov SN. Thermal inactivation of volume-sensitive K(+),Cl(-) cotransport and plasma membrane relief changes in human erythrocytes. Pflugers Arch. 2013;465(7):977–83.PubMedCrossRef
52.
Kato GJ, Piel FB, Reid CD, Gaston MH, Ohene-Frempong K, Krishnamurti L, et al. Sickle cell disease. Nat Rev Dis Primers. 2018;4:18010.PubMedCrossRef
53.
Yuditskaya S, Suffredini AF, Kato GJ. The proteome of sickle cell disease: insights from exploratory proteomic profiling. Expert Rev Proteomics. 2010;7(6):833–48.PubMedPubMedCentralCrossRef
54.
Brugnara C. Sickle cell dehydration: Pathophysiology and therapeutic applications. Clin Hemorheol Microcirc. 2018;68(2-3):187–204.PubMedCrossRef
55.
Brugnara C, Van Ha T, Tosteson DC. Role of chloride in potassium transport through a K-Cl cotransport system in human red blood cells. Am J Physiol. 1989;256(5 Pt 1):C994–1003.PubMedCrossRef
56.
Darrow MC, Zhang Y, Cinquin BP, Smith EA, Boudreau R, Rochat RH, et al. Visualizing red blood cell sickling and the effects of inhibition of sphingosine kinase 1 using soft X-ray tomography. J Cell Sci. 2016;129(18):3511–7.PubMedPubMedCentralCrossRef
57.
Gibson JS, Speake PF, Ellory JC. Differential oxygen sensitivity of the K+-Cl- cotransporter in normal and sickle human red blood cells. J Physiol. 1998;511(Pt 1):225–34.PubMedPubMedCentralCrossRef
58.
Gibson JS, Khan A, Speake PF, Ellory JC. O2 dependence of K+ transport in sickle cells: the effect of different cell populations and the substituted benzaldehyde 12C79. FASEB J. 2001;15(3):823–32.PubMedCrossRef
59.
Muzyamba MC, Campbell EH, Gibson JS. Effect of intracellular magnesium and oxygen tension on K+-Cl- cotransport in normal and sickle human red cells. Cell Physiol Biochem. 2006;17(3-4):121–8.PubMedCrossRef
60.
Gibson JS, Speake PF, Muzyamba MC, Husain F, Luckas MC, Ellory JC. K(+) transport in red blood cells from human umbilical cord. Biochim Biophys Acta. 2001;1512(2):231–8.PubMedCrossRef
61.
Gibson JS, Muzyamba MC, Ball SE, Ellory JC. K+ transport in HbSC-containing human red blood cells. Journal of Physiology. 2001;535:27.
62.
Ueda Y, Nagel RL, Bookchin RM. An increased Bohr effect in sickle cell anemia. Blood. 1979;53(3):472–80.PubMed
63.
Hannemann A, Weiss E, Rees DC, Dalibalta S, Ellory JC, Gibson JS. The Properties of Red Blood Cells from Patients Heterozygous for HbS and HbC (HbSC Genotype). Anemia. 2011;2011:248527.PubMedCrossRef
64.
Ellory JC, Hall AC, Ody SA. Factors affecting the activation and inactivation of KCl cotransport in 'young' human red cells. Biomed Biochim Acta. 1990;49(2-3):S64–9.PubMed
65.
Brugnara C, Bunn HF, Tosteson DC. Regulation of erythrocyte cation and water content in sickle cell anemia. Science. 1986;232(4748):388–90.PubMedCrossRef
66.
Gonsalves CS, Crable S, Chandra S, Li W, Kalra VK, Joiner CH. Angiogenic growth factors augment K-Cl cotransporter expression in erythroid cells via hypoxia-inducible factor-1alpha. Am J Hematol. 2014;89(3):273–81.PubMedCrossRef
67.
Gonsalves CS, Li C, Mpollo MS, Pullarkat V, Malik P, Tahara SM, et al. Erythropoietin-mediated expression of placenta growth factor is regulated via activation of hypoxia-inducible factor-1alpha and post-transcriptionally by miR-214 in sickle cell disease. Biochem J. 2015;468(3):409–23.PubMedCrossRef
68.
Ortiz OE, Lew VL, Bookchin RM. Deoxygenation permeabilizes sickle cell anaemia red cells to magnesium and reverses its gradient in the dense cells. J Physiol. 1990;427:211–26.PubMedPubMedCentralCrossRef
69.
Willcocks JP, Mulquiney PJ, Ellory JC, Veech RL, Radda GK, Clarke K. Simultaneous determination of low free Mg2+ and pH in human sickle cells using 31P NMR spectroscopy. J Biol Chem. 2002;277(51):49911–20.PubMedCrossRef
70.
De Franceschi L, Bachir D, Galacteros F, Tchernia G, Cynober T, Alper S, et al. Oral magnesium supplements reduce erythrocyte dehydration in patients with sickle cell disease. J Clin Invest. 1997;100(7):1847–52.PubMedPubMedCentralCrossRef
71.
Sachs JR. Soluble polycations and cationic amphiphiles inhibit volume-sensitive K-Cl cotransport in human red cell ghosts. Am J Physiol. 1994;266(4 Pt 1):C997–1005.PubMedCrossRef
72.
Orlov SN, Kolosova IA, Cragoe EJ, Gurlo TG, Mongin AA, Aksentsev SL, et al. Kinetics and peculiarities of thermal inactivation of volume-induced Na+/H+ exchange, Na+,K+,2Cl- cotransport and K+,Cl- cotransport in rat erythrocytes. Biochim Biophys Acta. 1993;1151(2):186–92.PubMedCrossRef
73.
de Los HP, Alessi DR, Gourlay R, Campbell DG, Deak M, Macartney TJ, et al. The WNK-regulated SPAK/OSR1 kinases directly phosphorylate and inhibit the K+-Cl- co-transporters. Biochem J. 2014;458(3):559–73.CrossRef
74.
Kahle KT, Flores B, Bharucha-Goebel D, Zhang J, Donkervoort S, Hegde M, et al. Peripheral motor neuropathy is associated with defective kinase regulation of the KCC3 cotransporter. Sci Signal. 2016;9(439):ra77.PubMedPubMedCentralCrossRef
75.
Melo Z, de los Heros P, Cruz-Rangel S, Vazquez N, Bobadilla NA, Pasantes-Morales H, et al. N-terminal serine dephosphorylation is required for KCC3 cotransporter full activation by cell swelling. J Biol Chem. 2013;288(44):31468–76.PubMedPubMedCentralCrossRef
76.
Mercado A, de Los HP, Melo Z, Chavez-Canales M, Murillo-de-Ozores AR, Moreno E, et al. With no lysine L-WNK1 isoforms are negative regulators of the K+-Cl- cotransporters. Am J Physiol Cell Physiol. 2016;311(1):C54–66.PubMedPubMedCentralCrossRef
77.
Xu B, English JM, Wilsbacher JL, Stippec S, Goldsmith EJ, Cobb MH. WNK1, a novel mammalian serine/threonine protein kinase lacking the catalytic lysine in subdomain II. J Biol Chem. 2000;275(22):16795–801.PubMedCrossRef
78.
Rinehart J, Kahle KT, de Los HP, Vazquez N, Meade P, Wilson FH, et al. WNK3 kinase is a positive regulator of NKCC2 and NCC, renal cation-Cl- cotransporters required for normal blood pressure homeostasis. Proc Natl Acad Sci U S A. 2005;102(46):16777–82.PubMedPubMedCentralCrossRef
79.
Sasaki E, Susa K, Mori T, Isobe K, Araki Y, Inoue Y, et al. KLHL3 Knockout Mice Reveal the Physiological Role of KLHL3 and the Pathophysiology of Pseudohypoaldosteronism Type II Caused by Mutant KLHL3. Mol Cell Biol. 2017;37(7):e00508–16.
80.
Glover M, Ware JS, Henry A, Wolley M, Walsh R, Wain LV, et al. Detection of mutations in KLHL3 and CUL3 in families with FHHt (familial hyperkalaemic hypertension or Gordon's syndrome). Clin Sci (Lond). 2014;126(10):721–6.PubMedPubMedCentralCrossRef
81.
82.
Lew VL, Ortiz OE, Bookchin RM. Stochastic nature and red cell population distribution of the sickling-induced Ca2+ permeability. J Clin Invest. 1997;99(11):2727–35.PubMedPubMedCentralCrossRef
83.
Ma YL, Rees DC, Gibson JS, Ellory JC. The conductance of red blood cells from sickle cell patients: ion selectivity and inhibitors. J Physiol. 2012;590(9):2095–105.PubMedPubMedCentralCrossRef
84.
Demolombe S, Duprat F, Honore E, Patel A. Slower Piezo1 inactivation in dehydrated hereditary stomatocytosis (xerocytosis). Biophys J. 2013;105(4):833–4.PubMedPubMedCentralCrossRef
85.
Cahalan SM, Lukacs V, Ranade SS, Chien S, Bandell M, Patapoutian A. Piezo1 links mechanical forces to red blood cell volume. Elife. 2015;4.
86.
Maher AD, Kuchel PW. The Gardos channel: a review of the Ca2+-activated K+ channel in human erythrocytes. Int J Biochem Cell Biol. 2003;35(8):1182–97.PubMedCrossRef
87.
Ataga KI, Smith WR, De Castro LM, Swerdlow P, Saunthararajah Y, Castro O, et al. Efficacy and safety of the Gardos channel blocker, senicapoc (ICA-17043), in patients with sickle cell anemia. Blood. 2008;111(8):3991–7.PubMedCrossRef
88.
Mohandas N, Rossi ME, Clark MR. Association between morphologic distortion of sickle cells and deoxygenation-induced cation permeability increase. Blood. 1986;68(2):450–4.PubMed
89.
Gardos G. The function of calcium in the potassium permeability of human erythrocytes. Biochim Biophys Acta. 1958;30(3):653–4.PubMedCrossRef
90.
Castro OL, Gordeuk VR, Gladwin MT, Steinberg MH. Senicapoc trial results support the existence of different sub-phenotypes of sickle cell disease with possible drug-induced phenotypic shifts. Br J Haematol. 2011;155(5):636–8.PubMedCrossRef
91.
McNaughton-Smith GA, Burns JF, Stocker JW, Rigdon GC, Creech C, Arrington S, et al. Novel inhibitors of the Gardos channel for the treatment of sickle cell disease. J Med Chem. 2008;51(4):976–82.PubMedCrossRef
92.
Shang C, Lu YM, Meng LR. KCC1 gene advances cell invasion ability by regulating ERK signaling pathway in endometrial cancer HEC-1B cell line. Int J Gynecol Cancer. 2011;21(5):795–9.PubMedCrossRef
93.
Yao M, Yoshida M, Kishida T, Nakaigawa N, Baba M, Kobayashi K, et al. VHL tumor suppressor gene alterations associated with good prognosis in sporadic clear-cell renal carcinoma. J Natl Cancer Inst. 2002;94(20):1569–75.PubMedCrossRef
94.
Patard JJ, Fergelot P, Karakiewicz PI, Klatte T, Trinh QD, Rioux-Leclercq N, et al. Low CAIX expression and absence of VHL gene mutation are associated with tumor aggressiveness and poor survival of clear cell renal cell carcinoma. Int J Cancer. 2008;123(2):395–400.PubMedPubMedCentralCrossRef
95.
Kornak U, Kasper D, Bosl MR, Kaiser E, Schweizer M, Schulz A, et al. Loss of the ClC-7 chloride channel leads to osteopetrosis in mice and man. Cell. 2001;104(2):205–15.PubMedCrossRef
96.
Feng S, Deng L, Chen W, Shao J, Xu G, Li YP. Atp6v1c1 is an essential component of the osteoclast proton pump and in F-actin ring formation in osteoclasts. Biochem J. 2009;417(1):195–203.PubMedCrossRef
97.
Baron R, Neff L, Roy C, Boisvert A, Caplan M. Evidence for a high and specific concentration of (Na+,K+)ATPase in the plasma membrane of the osteoclast. Cell. 1986;46(2):311–20.PubMedCrossRef
98.
Wu J, Glimcher LH, Aliprantis AO. HCO3-/Cl- anion exchanger SLC4A2 is required for proper osteoclast differentiation and function. Proc Natl Acad Sci U S A. 2008;105(44):16934–9.PubMedPubMedCentralCrossRef
99.
Cheng L, Zhang K, Zhang Z. Effectiveness of thiazides on serum and urinary calcium levels and bone mineral density in patients with osteoporosis: a systematic review and meta-analysis. Drug Des Devel Ther. 2018;12:3929–35.PubMedPubMedCentralCrossRef
100.
Hsu YJ, Yang SS, Cheng CJ, Liu ST, Huang SM, Chau T, et al. Thiazide-sensitive Na+ -Cl- cotransporter (NCC) gene inactivation results in increased duodenal Ca2+ absorption, enhanced osteoblast differentiation and elevated bone mineral density. J Bone Miner Res. 2015;30(1):116–27.PubMedCrossRef
101.
Alexander RT, Dimke H. Effect of diuretics on renal tubular transport of calcium and magnesium. Am J Physiol Renal Physiol. 2017;312(6):F998–F1015.PubMedCrossRef
102.
Dvorak MM, De Joussineau C, Carter DH, Pisitkun T, Knepper MA, Gamba G, et al. Thiazide diuretics directly induce osteoblast differentiation and mineralized nodule formation by interacting with a sodium chloride co-transporter in bone. J Am Soc Nephrol. 2007;18(9):2509–16.PubMedCrossRef
103.
Sun YT, Shieh CC, Delpire E, Shen MR. K(+)-Cl(-) cotransport mediates the bactericidal activity of neutrophils by regulating NADPH oxidase activation. J Physiol. 2012;590(14):3231–43.PubMedPubMedCentralCrossRef
104.
Foote JR, Behe P, Frampton M, Levine AP, Segal AW. An exploration of charge compensating ion channels across the phagocytic vacuole of neutrophils. Front Pharmacol. 2017;8:94.PubMedPubMedCentral
105.
Paredes J, Figueiredo J, Albergaria A, Oliveira P, Carvalho J, Ribeiro AS, et al. Epithelial E- and P-cadherins: role and clinical significance in cancer. Biochim Biophys Acta. 2012;1826(2):297–311.PubMed
Metadata
Title
K+-Cl− cotransporter 1 (KCC1): a housekeeping membrane protein that plays key supplemental roles in hematopoietic and cancer cells
Authors
A. P. Garneau
S. Slimani
L. E. Tremblay
M. J. Fiola
A. A. Marcoux
P. Isenring
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2019
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-019-0766-x

Other articles of this Issue 1/2019

Journal of Hematology & Oncology 1/2019 Go to the issue

Review

Next-generation sequencing for BCR-ABL1 kinase domain mutation testing in patients with chronic myeloid leukemia: a position paper

Review

CircRNAs in cancer metabolism: a review

Research

Glyphosate induces benign monoclonal gammopathy and promotes multiple myeloma progression in mice

Review

Pathogenesis and biomarkers of natural killer T cell lymphoma (NKTL)

Research

Measurable residual disease at myeloablative allogeneic transplantation in adults with acute lymphoblastic leukemia: a retrospective registry study on 2780 patients from the acute leukemia working party of the EBMT

Review

Engineering switchable and programmable universal CARs for CAR T therapy
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits