Chapter 11 : The CLC Family of Proteins: Chloride Transporters and Channels

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Several members of the CLC family of proteins are voltage-gated, and this entire family is sometimes termed the voltage-gated family of Cl channels (chloride channels). Bioinformatics screening of CLC channels suggests the existence of regions in the cytoplasmic carboxyl tail of these proteins that have the propensity to bind actin and possibly other cytoskeletal proteins. While the ClC-0, ClC-1, ClC-2, and ClC-Ka and -Kb branch of the CLC family are generally believed to be plasma membrane channels, the location of the others is controversial, being totally or partially confined to intracellular membranes under normal circumstances. The authors' recent analysis of the human promoter has identified several interesting consensus transcription-factor-binding sites. By mutation, their importance in the transcriptional regulation of this gene has been demonstrated. Transcription factor binding has been demonstrated, and the identification of these factors is under way. Mutations in CLC channels have now been associated with a number of diseases in both humans and other species. Myotonia, the best understood of the CLC diseases, is characterized by a peculiar muscle stiffness that is normally painless, an inability of the muscle to relax after a voluntary contraction. This is purely a muscle phenomenon and does not involve nerve dysfunction. It is sometimes accompanied by weakness, and the stiffness may improve after exercise. Genetic or pharmacological manipulation of the relevant Cl channels could treat CLC diseases or, conversely, mimicking some aspect of these diseases could point the way to therapies for other diseases.

Citation: Rickards H, Bartley P, Bretag A, Bagley C. 2005. The CLC Family of Proteins: Chloride Transporters and Channels, p 209-246. In Kubalski A, Martinac B (ed), Bacterial Ion Channels and Their Eukaryotic Homologs. ASM Press, Washington, DC. doi: 10.1128/9781555816452.ch11

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Image of Figure 1.
Figure 1.

Dual topological diagram comparing the original 12 hydrophobic domains with the 18 helices (A to R) based on the X-ray structure. The lengthy eukaryotic C tail of largely indeterminate structure with its pair of CBS domains is also compared with the short prokaryotic C tail. Original hydrophobic domain D13 coincides roughly with CBS2.

Citation: Rickards H, Bartley P, Bretag A, Bagley C. 2005. The CLC Family of Proteins: Chloride Transporters and Channels, p 209-246. In Kubalski A, Martinac B (ed), Bacterial Ion Channels and Their Eukaryotic Homologs. ASM Press, Washington, DC. doi: 10.1128/9781555816452.ch11
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Image of Figure 2.
Figure 2.

Illustration of CLC protein types in prokaryotes and eukaryotes. Prokaryotic ClC-Ec1 is shown as a Cl/H exchanger. Eukaryotes have evolved a variety of CLC proteins. Some are confined to internal membranes, where they are channels associated with proton pumps and endosome acidification. Others are plasma membrane channels capable of accommodating the current flow necessary to stabilize muscle membrane potentials or to facilitate the stunning voltage discharges of electric rays.

Citation: Rickards H, Bartley P, Bretag A, Bagley C. 2005. The CLC Family of Proteins: Chloride Transporters and Channels, p 209-246. In Kubalski A, Martinac B (ed), Bacterial Ion Channels and Their Eukaryotic Homologs. ASM Press, Washington, DC. doi: 10.1128/9781555816452.ch11
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Image of Figure 3.
Figure 3.

Diagram showing the relatedness of selected ClC sequences. Branch lengths are not proportional to evolutionary differences. Three main branches of the eukaryotic CLC family can be seen: that including ClC-0, ClC-1, ClC-2, ClC-Ka, and ClC-Kb; that including ClC-3, ClC-4, and ClC-5; and that including ClC-6 and ClC-7. Of the others, only those of the plant , the yeast and the two prokaryotic CLCs, for which the crystal structures are known, have been included.

Citation: Rickards H, Bartley P, Bretag A, Bagley C. 2005. The CLC Family of Proteins: Chloride Transporters and Channels, p 209-246. In Kubalski A, Martinac B (ed), Bacterial Ion Channels and Their Eukaryotic Homologs. ASM Press, Washington, DC. doi: 10.1128/9781555816452.ch11
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Image of Figure 4.
Figure 4.

Whole-cell patch-clamp currents recorded from cultured HEK cells expressing the wild-type (WT) or mutant (C278G) human skeletal muscle chloride channel, ClC-Hs1. (A) A sequence of currents is shown (overlying each other) in response to conditioning voltage steps from −140 mV (inside negative compared to outside zero) to +100 mV. “Tail” currents are also shown in response to a constant test pulse of −100 mV. From the sizes of the tail currents, an apparent overall (for both gates) open probability, , can be calculated for these channels at each conditioning voltage. (B) for the WT channels is shown. Separated apparent open probabilities for the fast and common gates are shown in panel D for the C278G mutant whose currents are recorded in panel C.

Citation: Rickards H, Bartley P, Bretag A, Bagley C. 2005. The CLC Family of Proteins: Chloride Transporters and Channels, p 209-246. In Kubalski A, Martinac B (ed), Bacterial Ion Channels and Their Eukaryotic Homologs. ASM Press, Washington, DC. doi: 10.1128/9781555816452.ch11
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Image of Figure 5.
Figure 5.

Whole-cell patch-clamp currents as in Fig 4 . It is apparent (A) that currents from the G284S mutant display almost purely fast gating, and (B) this is reinforced by the separated curves, where it can be seen that the for the common gates is close to 1 even at very negative potentials. (C) In complete contrast, mutant S289G seems to show only common (slow) gating. This is because, as the overall curve in panel D shows, the common gates do not begin to open in this mutant until around 0 mV, by which voltage the fast gates are fully open (cf. fast for G284S in panel B and for WT in Fig. 4B ).

Citation: Rickards H, Bartley P, Bretag A, Bagley C. 2005. The CLC Family of Proteins: Chloride Transporters and Channels, p 209-246. In Kubalski A, Martinac B (ed), Bacterial Ion Channels and Their Eukaryotic Homologs. ASM Press, Washington, DC. doi: 10.1128/9781555816452.ch11
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1. Accardi, A.,, and C. Miller. 2004. Secondary active transport mediated by a prokaryotic homologue of ClC Clchannels. Nature 427:803807.
2. Adachi, S.,, S. Uchida,, H. Ito,, M. Hata,, M. Hiroe,, F. Marumo,, and S. Sasaki. 1994. Two isoforms of a chloride channel predominantly expressed in thick ascending limb of Henle’s loop and collecting ducts of rat kidney. J. Biol. Chem. 269:1767717683.
3. Adams, J.,, Z. P. Chen,, B. J. Van Denderen,, C. J. Morton,, M. W. Parker,, L. A. Witters,, D. Stapleton,, and B. E. Kemp. 2004. Intrasteric control of AMPK via the gamma1 subunit AMP allosteric regulatory site. Protein Sci. 13:155165.
4. Aromataris, E. C.,, D. S. Astill,, G. Y. Rychkov,, S. H. Bryant,, A. H. Bretag,, and M. L. Roberts. 1999. Modulation of the gating of ClC-1 by S-(-) 2-(4-chlorophenoxy) propionic acid. Br. J. Pharmacol. 126:13751382.
5. Aromataris, E. C.,, G. Y. Rychkov,, B. Bennetts,, B. P. Hughes,, A. H. Bretag,, and M. L. Roberts. 2001. Fast and slow gating of CLC-1: differential effects of 2-(4-chlorophenoxy) propionic acid and dominant negative mutations. Mol. Pharmacol. 60:200208.
6. Beck, C. L.,, C. Fahlke,, and A. L. George, Jr. 1996. Molecular basis for decreased muscle chloride conductance in the myotonic goat. Proc. Natl. Acad. Sci. USA 93:1124811252.
7. Bennetts, B.,, M. L. Roberts,, A. H. Bretag,, and G. Y. Rychkov. 2001. Temperature dependence of human muscle ClC-1 chloride channel. J. Physiol. 535:8393.
8. Bianchi, L.,, D. M. Miller III,, and A. L. GeorgeJr., 2001. Expression of a ClC chloride channel in Caenorhabditis elegans gamma-aminobutyric acid-ergic neurons. Neurosci. Lett. 299:177180.
9. Bösl, M. R.,, V. Stein,, C. Hübner,, A. A. Zdebik,, S. E. Jordt,, A. K. Mukhopadhyay,, M. S. Davidoff,, A. F. Holstein,, and T. J. Jentsch. 2001. Male germ cells and photoreceptors, both dependent on close cell-cell interactions, degenerate upon ClC-2 Cl- channel disruption. EMBO J. 20:12891299.
10. Boyle, P. J.,, and E. J. Conway. 1941. Potassium accumulation in muscle and associated changes. J. Physiol. Lond. 100:163.
11. Brakeman, P. R.,, A. A. Lanahan,, R. O’Brien,, K. Roche,, C. A. Barnes,, R. L. Huganir,, and P. F. Worley. 1997. Homer: a protein that selectively binds metabotropic glutamate receptors. Nature 386:284288.
12. Brandt, S.,, and T. J. Jentsch. 1995. ClC-6 and ClC-7 are two novel broadly expressed members of the CLC chloride channel family. FEBS Lett. 377:1520.
13. Bretag, A. H. 1983. Antimyotonic agents and myotonia. Proc. Aust. Physiol. Pharmacol. Soc. 14:170191.
14. Bretag, A. H. 1987. Muscle chloride channels. Physiol. Rev. 67:618724.
15. Brinkmeier, H.,, and H. Jockusch. 1987. Activators of protein kinase C induce myotonia by lowering chloride conductance in muscle. Biochem. Biophys. Res. Commun. 148:13831389.
16. Bryant, S. H.,, and D. Conte-Camerino. 1991. Chloride channel regulation in the skeletal muscle of normal and myotonic goats. Pflugers Arch. 417:605610.
17. Bryant, S. H.,, and A. Morales-Aguilera. 1971. Chloride conductance in normal and myotonic muscle fibres and the action of monocarboxylic aromatic acids. J. Physiol. 219:367383.
18. Buyse, G.,, D. Trouet,, T. Voets,, L. Missiaen,, G. Droogmans,, B. Nilius,, and J. Eggermont. 1998. Evidence for the intracellular location of chloride channel (ClC)-type proteins: co-localization of ClC-6a and ClC-6c with the sarco/endoplasmic-reticulum Ca2+ pump SERCA2b. Biochem. J. 330:10151021.
19. Campos-Xavier, A. B.,, J. M. Saraiva,, L. M. Ribeiro,, A. Munnich,, and V. Cormier-Daire. 2003. Chloride channel 7 (CLCN7) gene mutations in intermediate autosomal recessive osteopetrosis. Hum. Genet. 112:186189.
20. Chen, M. F.,, and T. Y. Chen. 2003. Side-chain charge effects and conductance determinants in the pore of ClC-0 chloride channels. J. Gen. Physiol. 122:133145.
21. Chen, T. Y.,, and C. Miller. 1996. Nonequilibrium gating and voltage dependence of the ClC-0 Cl-channel. J. Gen. Physiol. 108:237250.
22. Cleiren, E.,, O. Bénichou,, E. Van Hul,, J. Gram,, J. Bollerslev,, F. R. Singer,, K. Beaverson,, A. Aledo,, M. P. Whyte,, T. Yoneyama,, M. C. deVernejoul,, and W. Van Hul. 2001. Albers-Schönberg disease (autosomal dominant osteopetrosis, type II) results from mutations in the ClCN7 chloride channel gene. Hum. Mol. Genet. 10: 28612867.
23. De Luca, A.,, S. Pierno,, D. Cocchi,, and D. Conte Camerino. 1997. Effects of chronic growth hormone treatment in aged rats on the biophysical and pharmacological properties of skeletal muscle chloride channels. Br. J. Pharmacol. 121:369374.
24. Denton, J.,, K. Nehrke,, E. Rutledge,, R. Morrison,, and K. Strange. 2004. Alternative splicing of N- and C-termini of a C. elegans ClC channel alters gating and sensitivity to external Cl- and H+. J. Physiol. 555:97114.
25. Devuyst, O.,, P. T. Christie,, P. J. Courtoy,, R. Beauwens,, and R. V. Thakker. 1999. Intra-renal and subcellular distribution of the human chloride channel, CLC-5, reveals a pathophysiological basis for Dent’s disease. Hum. Mol. Genet. 8:247257.
26. Dhani, S. U.,, R. Mohammad-Panah,, N. Ahmed,, C. Ackerley,, M. Ramjeesingh,, and C. E. Bear. 2003. Evidence for a functional interaction between the ClC-2 chloride channel and the retrograde motor dynein complex. J. Biol. Chem. 278:1626216270.
27. Dick, G. M.,, K. K. Bradley,, B. Horowitz,, J. R. Hume,, and K. M. Sanders. 1998. Functional and molecular identification of a novel chloride conductance in canine colonic smooth muscle. Am. J. Physiol. 275:C940C950.
28. Dickerson, L. W.,, D. J. Bonthius,, B. C. Schutte,, B. Yang,, T. J. Barna,, M. C. Bailey,, K. Nehrke,, R. A. Williamson,, and F. S. Lamb. 2002. Altered GABAergic function accompanies hippocampal degeneration in mice lacking ClC-3 voltage-gated chloride channels. Brain Res. 958:227250.
29. Diewald, L.,, J. Rupp,, M. Dreger,, F. Hucho,, C. Gillen,, and H. Nawrath. 2002. Activation by acidic pH of CLC-7 expressed in oocytes from Xenopus laevis. Biochem. Biophys. Res. Commun. 291:421424.
30. Dogovski, C.,, J. Pi,, and A. J. Pittard. 2003. Putative interhelical interactions within the PheP protein revealed by second-site suppressor analysis. J. Bacteriol. 185:62256232.
31. Duan, D.,, S. Cowley,, B. Horowitz,, and J. R. Hume. 1999. A serine residue in ClC-3 links phosphorylationdephosphorylation to chloride channel regulation by cell volume. J. Gen. Physiol. 113:5770.
32. Duan, D.,, C. Winter,, S. Cowley,, J. R. Hume,, and B. Horowitz. 1997. Molecular identification of a volumeregulated chloride channel. Nature 390:417421.
33. Duffield, M.,, G. Rychkov,, A. Bretag,, and M. Roberts. 2003. Involvement of helices at the dimer interface in ClC-1 common gating. J. Gen. Physiol. 121:149161.
34. Dutzler, R.,, E. B. Campbell,, M. Cadene,, B. T. Chait,, and R. MacKinnon. 2002. X-ray structure of a ClC chloride channel at 3.0 Å reveals the molecular basis of anion selectivity. Nature 415:287294.
35. Dutzler, R.,, E. B. Campbell,, and R. MacKinnon. 2003. Gating the selectivity filter in ClC chloride channels. Science 300:108112.
36. Estévez, R.,, T. Boettger,, V. Stein,, R. Birkenhäger,, E. Otto,, F. Hildebrandt,, and T. J. Jentsch. 2001. Barttin is a Cl+ channel beta-subunit crucial for renal Cl- reabsorption and inner ear K+ secretion. Nature 414:558561.
37. Estévez, R.,, M. Pusch,, C. Ferrer-Costa,, M. Orozco,, and T. J. Jentsch. 2004. Functional and structural conservation of CBS domains from CLC chloride channels. J. Physiol. 557:363378.
38. Estévez, R.,, B. C. Schroeder,, A. Accardi,, T. J. Jentsch,, and M. Pusch. 2003. Conservation of chloride channel structure revealed by an inhibitor binding site in ClC-1. Neuron 38:4759.
39. Fahlke, C.,, T. Knittle,, C. A. Gurnett,, K. P. Campbell,, and A. L. George, Jr. 1997. Subunit stoichiometry of human muscle chloride channels. J. Gen. Physiol. 109:93104.
40. Fahlke, C.,, A. Rosenbohm,, N. Mitrovic,, A. L. George, Jr.,, and R. Rüdel. 1996. Mechanism of voltagedependent gating in skeletal muscle chloride channels. Biophys. J. 71:695706.
41. Fahlke, C.,, R. Rüdel,, N. Mitrovic,, M. Zhou,, and A. L. George, Jr. 1995. An aspartic acid residue important for voltage-dependent gating of human muscle chloride channels. Neuron 15:463472.
42. Fisher, S. E.,, G. C. Black,, S. E. Lloyd,, E. Hatchwell,, O. Wrong,, R. V. Thakker,, and I. W. Craig. 1994. Isolation and partial characterization of a chloride channel gene which is expressed in kidney and is a candidate for Dent’s disease (an X-linked hereditary nephrolithiasis). Hum. Mol. Genet. 3:20532059.
43. Fong, P.,, A. Rehfeldt,, and T. J. Jentsch. 1998. Determinants of slow gating in ClC-0, the voltage-gated chloride channel of Torpedo marmorata. Am. J. Physiol. 274:C966C973.
44. Foskett, J. K. 1998. ClC and CFTR chloride channel gating. Annu. Rev. Physiol. 60:689717.
45. Frattini, A.,, P. J. Orchard,, C. Sobacchi,, S. Giliani,, M. Abinun,, J. P. Mattsson,, D. J. Keeling,, A. K. Andersson,, P. Wallbrandt,, L. Zecca,, L. D. Notarangelo,, P. Vezzoni,, and A. Villa. 2000. Defects in TCIRG1 subunit of the vacuolar proton pump are responsible for a subset of human autosomal recessive osteopetrosis. Nat. Genet. 25:343346.
46. Frattini, A.,, A. Pangrazio,, L. Susani,, C. Sobacchi,, M. Mirolo,, M. Abinun,, M. Andolina,, A. Flanagan,, E. M. Horwitz,, E. Mihci,, L. D. Notarangelo,, U. Ramenghi,, A. Teti,, J. Van Hove,, D. Vujic,, T. Young,, A. Albertini,, P. J. Orchard,, P. Vezzoni,, and A. Villa. 2003. Chloride channel ClCN7 mutations are responsible for severe recessive, dominant, and intermediate osteopetrosis. J. Bone Miner. Res. 18:17401747.
47. Friedrich, T.,, T. Breiderhoff,, and T. J. Jentsch. 1999. Mutational analysis demonstrates that ClC-4 and ClC-5 directly mediate plasma membrane currents. J. Biol. Chem. 274:896902.
48. Fujita, N.,, H. Mori,, T. Yura,, and A. Ishihama. 1994. Systematic sequencing of the Escherichia coli genome: analysis of the 2.4-4.1 min (110,917-193,643 bp) region. Nucleic Acids Res. 22:16371639.
49. Furukawa, T.,, T. Ogura,, Y. J. Zheng,, H. Tsuchiya,, H. Nakaya,, Y. Katayama,, and N. Inagaki. 2002. Phosphorylation and functional regulation of ClC-2 chloride channels expressed in Xenopus oocytes by M cyclindependent protein kinase. J. Physiol. 540:883893.
50. Gaxiola, R. A.,, D. S. Yuan,, R. D. Klausner,, and G. R. Fink. 1998. The yeast CLC chloride channel functions in cation homeostasis. Proc. Natl. Acad. Sci. USA 95:40464050.
51. Geelen, D.,, C. Lurin,, D. Bouchez,, J. M. Frachisse,, F. Leliévre,, B. Courtial,, H. Barbier-Brygoo,, and C. Maurel. 2000. Disruption of putative anion channel gene AtCLC-a in Arabidopsis suggests a role in the regulation of nitrate content. Plant J. 21:259267.
52. Gentzsch, M.,, L. Cui,, A. Mengos,, X. B. Chang,, J. H. Chen,, and J. R. Riordan. 2003. The PDZ-binding chloride channel ClC-3B localizes to the Golgi and associates with cystic fibrosis transmembrane conductance regulator-interacting PDZ proteins. J. Biol. Chem. 278:64406449.
53. Greene, J. R.,, N. H. Brown,, B. J. DiDomenico,, J. Kaplan,, and D. J. Eide. 1993. The GEF1 gene of Saccharomyces cerevisiae encodes an integral membrane protein; mutations in which have effects on respiration and iron-limited growth. Mol. Gen. Genet. 241:542553.
54. Gründer, S.,, A. Thiemann,, M. Pusch,, and T. J. Jentsch. 1992. Regions involved in the opening of ClC-2 chloride channel by voltage and cell volume. Nature 360:759762.
55. Gyömörey, K.,, H. Yeger,, C. Ackerley,, E. Garami,, and C. E. Bear. 2000. Expression of the chloride channel ClC-2 in the murine small intestine epithelium. Am. J. Physiol. Cell. Physiol. 279:C1787C1794.
56. Hanke, W.,, and C. Miller. 1983. Single chloride channels from Torpedo electroplax. Activation by protons. J. Gen. Physiol. 82:2545.
57. Haug, K.,, M. Warnstedt,, A. K. Alekov,, T. Sander,, A. Ramirez,, B. Poser,, S. Maljevic,, S. Hebeisen,, C. Kubisch,, J. Rebstock,, S. Horvath,, K. Hallmann,, J. S. Dullinger,, B. Rau,, F. Haverkamp,, S. Beyenburg,, H. Schulz,, D. Janz,, B. Giese,, G. Müller-Newen,, P. Propping,, C. E. Elger,, C. Fahlke,, H. Lerche,, and A. Heils. 2003. Mutations in CLCN2 encoding a voltage-gated chloride channel are associated with idiopathic generalized epilepsies. Nat. Genet. 33:527532.
58. Hayama, A.,, S. Uchida,, S. Sasaki,, and F. Marumo. 2000. Isolation and characterization of the human CLC-5 chloride channel gene promoter. Gene 261:355364.
59. Hebeisen, S.,, A. Biela,, B. Giese,, G. Müller-Newen,, P. Hidalgo,, and C. Fahlke. 2004. The role of the carboxyl terminus in ClC chloride channel function. J. Biol. Chem. 279:1314013147.
60. Hechenberger, M.,, B. Schwappach,, W. N. Fischer,, W. B. Frommer,, T. J. Jentsch,, and K. Steinmeyer. 1996. A family of putative chloride channels from Arabidopsis and functional complementation of a yeast strain with a CLC gene disruption. J. Biol. Chem. 271:3363233638.
61. Henriksen, K.,, J. Gram,, S. Schaller,, B. H. Dahl,, M. H. Dziegiel,, J. Bollerslev,, and M. A. Karsdal. 2004. Characterization of osteoclasts from patients harboring a G215R mutation in ClC-7 causing autosomal dominant osteopetrosis type II. Am. J. Pathol. 164:15371545.
62. Hill, J. A., Jr.,, R. Coronado,, and H. C. Strauss. 1989. Reconstitution of ionic channels from human heart. J. Mol. Cell. Cardiol. 21:315322.
63. Hille, B. 2001. Ion Channels of Excitable Membranes, 3rd ed. Sinauer Associates, Sunderland, Mass.
64. Holmes, K. W.,, R. Hales,, S. Chu,, M. J. Maxwell,, P. J. Mogayzel, Jr.,, and P. L. Zeitlin. 2003. Modulation of Sp1 and Sp3 in lung epithelial cells regulates ClC-2 chloride channel expression. Am. J. Respir. Cell. Mol. Biol. 29:499505.
65. Hryciw, D. H.,, G. Y. Rychkov,, B. P. Hughes,, and A. H. Bretag. 1998. Relevance of the D13 region to the function of the skeletal muscle chloride channel, ClC-1. J. Biol. Chem. 273:43044307.
66. Hryciw, D. H.,, Y. Wang,, O. Devuyst,, C. A. Pollock,, P. Poronnik,, and W. B. Guggino. 2003. Cofilin interacts with ClC-5 and regulates albumin uptake in proximal tubule cell lines. J. Biol. Chem. 278:4016940176.
67. Hutter, O. F.,, and A. E. Warner. 1967a. The pH sensitivity of the chloride conductance of frog skeletal muscle. J. Physiol. 189:403425.
68. Hutter, O. F.,, and A. E. Warner. 1967b. Action of some foreign cations and anions on the chloride permeability of frog muscle. J. Physiol. 189:445460.
69. Iyer, R.,, T. M. Iverson,, A. Accardi,, and C. Miller. 2002. A biological role for prokaryotic ClC chloride channels. Nature 419:715718.
70. Javadpour, M. M.,, M. Eilers,, M. Groesbeek,, and S. O. Smith. 1999. Helix packing in polytopic membrane proteins: role of glycine in transmembrane helix association. Biophys. J. 77:16091618.
71. Jentsch, T. J.,, W. Günther,, M. Pusch,, and B. Schwappach. 1995. Properties of voltage-gated chloride channels of the ClC gene family. J. Physiol. 482:19S25S.
72. Jentsch, T. J.,, M. Pusch,, A. Rehfeldt,, and K. Steinmeyer. 1993. The ClC family of voltage-gated chloride channels: structure and function. Ann. N. Y. Acad. Sci. 707:285293.
73. Jentsch, T. J.,, K. Steinmeyer,, and G. Schwarz. 1990. Primary structure of Torpedo marmorata chloride channel isolated by expression cloning in Xenopus oocytes. Nature 348:510514.
74. Jin, N. G.,, J. K. Kim,, D. K. Yang,, S. J. Cho,, J. M. Kim,, E. J. Koh,, H. C. Jung,, I. So,, and K. W. Kim. 2003. Fundamental role of ClC-3 in volume-sensitive Cl- channel function and cell volume regulation in AGS cells. Am. J. Physiol. Gastrointest. Liver Physiol. 285:G938G948.
75. Jordt, S. E.,, and T. J. Jentsch. 1997. Molecular dissection of gating in the ClC-2 chloride channel. EMBO J. 16:15821592.
76. Kato, A.,, F. Ozawa,, Y. Saitoh,, K. Hirai,, and K. Inokuchi. 1997. vesl, a gene encoding VASP/Ena family related protein, is upregulated during seizure, long-term potentiation and synaptogenesis. FEBS Lett. 412:183189.
77. Kawasaki, M.,, T. Fukuma,, K. Yamauchi,, H. Sakamoto,, F. Marumo,, and S. Sasaki. 1999. Identification of an acid-activated Cl- channel from human skeletal muscles. Am. J. Physiol. 277:C948C954.
78. Kawasaki, M.,, S. Uchida,, T. Monkawa,, A. Miyawaki,, K. Mikoshiba,, F. Marumo,, and S. Sasaki. 1994. Cloning and expression of a protein kinase C-regulated chloride channel abundantly expressed in rat brain neuronal cells. Neuron 12:597604.
79. Kay, B. K.,, M. P. Williamson,, and M. Sudol. 2000. The importance of being proline: the interaction of prolinerich motifs in signaling proteins with their cognate domains. FASEB J. 14:231241.
80. Kirk, K. L. 2000. Chloride channels and tight junctions. Focus on “Expression of the chloride channel ClC-2 in the murine small intestine epithelium.” Am. J. Physiol. Cell Physiol. 279:C1675C1676.
81. Klocke, R.,, K. Steinmeyer,, T. J. Jentsch,, and H. Jockusch. 1994. Role of innervation, excitability, and myogenic factors in the expression of the muscular chloride channel ClC-1. A study on normal and myotonic muscle. J. Biol. Chem. 269:2763527639.
82. Koch, M. C.,, K. Steinmeyer,, C. Lorenz,, K. Ricker,, F. Wolf,, M. Otto,, B. Zoll,, F. Lehmann-Horn,, K. H. Grzeschik,, and T. J. Jentsch. 1992. The skeletal muscle chloride channel in dominant and recessive human myotonia. Science 257:797800.
83. Kornak, U.,, M. R. Bösl,, and C. Kubisch. 1999. Complete genomic structure of the CLCN6 and CLCN7 putative chloride channel genes(1). Biochim. Biophys. Acta 1447:100106.
84. Kornak, U.,, D. Kasper,, M. R. Bösl,, E. Kaiser,, M. Schweizer,, A. Schulz,, W. Friedrich,, G. Delling,, and T. J. Jentsch. 2001. Loss of the ClC-7 chloride channel leads to osteopetrosis in mice and man. Cell 104:205215.
85. Kubisch, C.,, T. Schmidt-Rose,, B. Fontaine,, A. H. Bretag,, and T. J. Jentsch. 1998. ClC-1 chloride channel mutations in myotonia congenita: variable penetrance of mutations shifting the voltage dependence. Hum. Mol. Genet. 7:17531760.
86. Lamb, F. S.,, G. H. Clayton,, B. X. Liu,, R. L. Smith,, T. J. Barna,, and B. C. Schutte. 1999. Expression of CLCN voltage-gated chloride channel genes in human blood vessels. J. Mol. Cell. Cardiol. 31:657666.
87. Lemmon, M. A.,, H. R. Treutlein,, P. D. Adams,, A. T. Brünger,, and D. M. Engelman. 1994. A dimerization motif for transmembrane alpha-helices. Nat. Struct. Biol. 1:157163.
88. Letizia, C.,, A. Taranta,, S. Migliaccio,, C. Caliumi,, D. Diacinti,, E. Delfini,, E. D’Erasmo,, M. Iacobini,, M. Roggini,, O. M. Albagha,, S. H. Ralston,, and A. Teti. 2004. Type II benign osteopetrosis (Albers-Schönberg disease) caused by a novel mutation in CLCN7 presenting with unusual clinical manifestations. Calcif. Tissue Int. 74:4246.
89. Liantonio, A.,, M. Pusch,, A. Picollo,, P. Guida,, A. De Luca,, S. Pierno,, G. Fracchiolla,, F. Loiodice,, P. Tortorella,, and D. Conte Camerino. 2004. Investigations of pharmacologic properties of the renal CLC-K1 chloride channel co-expressed with barttin by the use of 2-(p-chlorophenoxy)propionic acid derivatives and other structurally unrelated chloride channels blockers. J. Am. Soc. Nephrol. 15:1320.
90. Lipicky, R. J.,, and S. H. Bryant. 1966. Sodium, potassium, and chloride fluxes in intercostal muscle from normal goats and goats with hereditary myotonia. J. Gen. Physiol. 50:89111.
91. Lorenz, C.,, C. Meyer-Kleine,, K. Steinmeyer,, M. C. Koch,, and T. J. Jentsch. 1994. Genomic organization of the human muscle chloride channel ClC-1 and analysis of novel mutations leading to Becker-type myotonia. Hum. Mol. Genet. 3:941946.
92. Ludewig, U.,, T. J. Jentsch,, and M. Pusch. 1997a. Inward rectification in ClC-0 chloride channels caused by mutations in several protein regions. J. Gen. Physiol. 110:165171.
93. Ludewig, U.,, T. J. Jentsch,, and M. Pusch. 1997b. Analysis of a protein region involved in permeation and gating of the voltage-gated Torpedo chloride channel ClC-0. J. Physiol. 498:691702.
94. Ludewig, U.,, M. Pusch,, and T. J. Jentsch. 1997c. Independent gating of single pores in CLC-0 chloride channels. Biophys. J. 73:789797.
95. Ludewig, U.,, M. Pusch,, and T. J. Jentsch. 1996. Two physically distinct pores in the dimeric ClC-0 chloride channel. Nature 383:340343.
96. Lurin, C.,, J. Güclü,, C. Cheniclet,, J. P. Carde,, H. Barbier-Brygoo,, and C. Maurel. 2000. CLC-Nt1, a putative chloride channel protein of tobacco, co-localizes with mitochondrial membrane markers. Biochem. J. 348(Part 2):291295.
97. Luyckx, V. A.,, F. O. Goda,, D. B. Mount,, T. Nishio,, A. Hall,, S. C. Hebert,, T. G. Hammond,, and A. S. Yu. 1998. Intrarenal and subcellular localization of rat CLC5. Am. J. Physiol. 275:F761F769.
98. Maduke, M.,, C. Williams,, and C. Miller. 1998. Formation of CLC-0 chloride channels from separated transmembrane and cytoplasmic domains. Biochemistry 37:13151321.
99. Malinowska, D. H.,, E. Y. Kupert,, A. Bahinski,, A. M. Sherry,, and J. Cuppoletti. 1995. Cloning, functional expression, and characterization of a PKA-activated gastric Cl- channel. Am. J. Physiol. 268:C191C200.
100. Matsumura, Y.,, S. Uchida,, Y. Kondo,, H. Miyazaki,, S. B. Ko,, A. Hayama,, T. Morimoto,, W. Liu,, M. Arisawa,, S. Sasaki,, and F. Marumo. 1999. Overt nephrogenic diabetes insipidus in mice lacking the CLC-K1 chloride channel. Nat. Genet. 21:9598.
101. Mehrke, G.,, H. Brinkmeier,, and H. Jockusch. 1988. The myotonic mouse mutant ADR: electrophysiology of the muscle fiber. Muscle Nerve 11:440446.
102. Meyer-Kleine, C.,, K. Steinmeyer,, K. Ricker,, T. J. Jentsch,, and M. C. Koch. 1995. Spectrum of mutations in the major human skeletal muscle chloride channel gene (CLCN1) leading to myotonia. Am. J. Hum. Genet. 57:13251334.
103. Middleton, R. E.,, D. J. Pheasant,, and C. Miller. 1996. Homodimeric architecture of a ClC-type chloride ion channel. Nature 383:337340.
104. Miller, C. 1983. Integral membrane channels: studies in model membranes. Physiol. Rev. 63:12091242.
105. Miller, C.,, and M. M. White. 1984. Dimeric structure of single chloride channels from Torpedo electroplax. Proc. Natl. Acad. Sci. USA 81:27722775.
106. Mindell, J. A.,, and M. Maduke. 2001. ClC chloride channels. Genome Biol. 2:REVIEWS 3003.1-3003.6.
107. Mo, L.,, W. Xiong,, T. Qian,, H. Sun,, and N. K. Wills. 2004. Coexpression of complementary fragments of ClC-5 and restoration of chloride channel function in a Dent’s disease mutation. Am. J. Physiol. Cell Physiol. 286:C79C89.
108. Mohammad-Panah, R.,, C. Ackerley,, J. Rommens,, M. Choudhury,, Y. Wang,, and C. E. Bear. 2002. The chloride channel ClC-4 co-localizes with cystic fibrosis transmembrane conductance regulator and may mediate chloride flux across the apical membrane of intestinal epithelia. J. Biol. Chem. 277:566574.
109. Murray, C. B.,, S. Chu,, and P. L. Zeitlin. 1996. Gestational and tissue-specific regulation of C1C-2 chloride channel expression. Am. J. Physiol. 271:L829L837.
110. Nagamitsu, S.,, T. Matsuura,, M. Khajavi,, R. Armstrong,, C. Gooch,, Y. Harati,, and T. Ashizawa. 2000. A “dystrophic” variant of autosomal recessive myotonia congenita caused by novel mutations in the CLCN1 gene. Neurology 55:16971703.
111. Nehrke, K.,, T. Begenisich,, J. Pilato,, and J. E. Melvin. 2000. Into ion channel and transporter function. Caenorhabditis elegans ClC-type chloride channels: novel variants and functional expression. Am. J. Physiol. Cell Physiol. 279:C2052C2066.
112. Obermüller, N.,, N. Gretz,, W. Kriz,, R. F. Reilly,, and R. Witzgall. 1998. The swelling-activated chloride channel ClC-2, the chloride channel ClC-3, and ClC-5, a chloride channel mutated in kidney stone disease, are expressed in distinct subpopulations of renal epithelial cells. J. Clin. Investig. 101:635642.
113. Ogura, T.,, T. Furukawa,, T. Toyozaki,, K. Yamada,, Y. J. Zheng,, Y. Katayama,, H. Nakaya,, and N. Inagaki. 2002. ClC-3B, a novel ClC-3 splicing variant that interacts with EBP50 and facilitates expression of CFTRregulated ORCC. FASEB J. 16:863865.
114. O’Neill, G. P.,, R. Grygorczyk,, M. Adam,, and A. W. Ford-Hutchinson. 1991. The nucleotide sequence of a voltage-gated chloride channel from the electric organ of Torpedo californica. Biochim. Biophys. Acta 1129:131134.
115. Palade, P. T.,, and R. L. Barchi. 1977. Characteristics of the chloride conductance in muscle fibers of the rat diaphragm. J. Gen. Physiol. 69:325342.
116. Paunola, E.,, P. K. Mattila,, and P. Lappalainen. 2002. WH2 domain: a small, versatile adapter for actin monomers. FEBS Lett. 513:9297.
117. Petalcorin, M. I.,, T. Oka,, M. Koga,, K. Ogura,, Y. Wada,, Y. Ohshima,, and M. Futai. 1999. Disruption of clh-1, a chloride channel gene, results in a wider body of Caenorhabditis elegans. J. Mol. Biol. 294:347355.
118. Ponting, C. P. 1997. CBS domains in ClC chloride channels implicated in myotonia and nephrolithiasis (kidney stones). J. Mol. Med. 75:160163.
119. Pusch, M. 2002. Myotonia caused by mutations in the muscle chloride channel gene CLCN1. Hum. Mutat. 19:423434.
120. Pusch, M.,, and T. J. Jentsch. 1994. Molecular physiology of voltage-gated chloride channels. Physiol. Rev. 74:813827.
121. Pusch, M.,, U. Ludewig,, and T. J. Jentsch. 1997. Temperature dependence of fast and slow gating relaxations of ClC-0 chloride channels. J. Gen. Physiol. 109:105116.
122. Pusch, M.,, U. Ludewig,, A. Rehfeldt,, and T. J. Jentsch. 1995. Gating of the voltage-dependent chloride channel ClC-0 by the permeant anion. Nature 373:527531.
123. Pusch, M.,, K. Steinmeyer,, and T. J. Jentsch. 1994. Low single channel conductance of the major skeletal muscle chloride channel, ClC-1. Biophys. J. 66:149152.
124. Rai, T.,, S. Uchida,, S. Sasaki,, and F. Marumo. 1999. Isolation and characterization of kidney-specific CLC-K2 chloride channel gene promoter. Biochem. Biophys. Res. Commun. 261:432438.
125. Rhodes, T. H.,, C. H. Vite,, U. Giger,, D. F. Patterson,, C. Fahlke,, and A. L. George, Jr. 1999. A missense mutation in canine C1C-1 causes recessive myotonia congenita in the dog. FEBS Lett. 456:5458.
126. Richard, E. A.,, and C. Miller. 1990. Steady-state coupling of ion-channel conformations to a transmembrane ion gradient. Science 247:12081210.
127. Rosenbohm, A.,, R. Rüdel,, and C. Fahlke. 1999. Regulation of the human skeletal muscle chloride channel hClC-1 by protein kinase C. J. Physiol. 514:677685.
128. Russ, W. P.,, and D. M. Engelman. 2000. The GxxxG motif: a framework for transmembrane helix-helix association. J. Mol. Biol. 296:911919.
129. Rutledge, E.,, L. Bianchi,, M. Christensen,, C. Boehmer,, R. Morrison,, A. Broslat,, A. M. Beld,, A. L. George,, D. Greenstein,, and K. Strange. 2001. CLH-3, a ClC-2 anion channel ortholog activated during meiotic maturation in C. elegans oocytes. Curr. Biol. 11:161170.
130. Rutledge, E.,, J. Denton,, and K. Strange. 2002. Cell cycle- and swelling-induced activation of a Caenorhabditis elegans ClC channel is mediated by CeGLC-7alpha/beta phosphatases. J. Cell Biol. 158:435444.
131. Rychkov, G. Y.,, D. S. Astill,, B. Bennetts,, B. P. Hughes,, A. H. Bretag,, and M. L. Roberts. 1997. pH-dependent interactions of Cd2+ and a carboxylate blocker with the rat C1C-1 chloride channel and its R304E mutant in the Sf-9 insect cell line. J. Physiol. 501:355362.
132. Rychkov, G. Y.,, M. Pusch,, D. S. Astill,, M. L. Roberts,, T. J. Jentsch,, and A. H. Bretag. 1996. Concentration and pH dependence of skeletal muscle chloride channel ClC-1. J. Physiol. 497:423435.
133. Rychkov, G. Y.,, M. Pusch,, M. L. Roberts,, T. J. Jentsch,, and A. H. Bretag. 1998. Permeation and block of the skeletal muscle chloride channel, ClC-1, by foreign anions. J. Gen. Physiol. 111:653665.
134. Sakamoto, H.,, M. Kawasaki,, S. Uchida,, S. Sasaki,, and F. Marumo. 1996. Identification of a new outwardly rectifying Cl- channel that belongs to a subfamily of the ClC Cl- channels. J. Biol. Chem. 271: 1021010216.
135. Sansom, M. S.,, and H. Weinstein. 2000. Hinges, swivels and switches: the role of prolines in signalling via transmembrane alpha-helices. Trends Pharmacol. Sci. 21:445451.
136. Schaller, S.,, K. Henriksen,, C. Sveigaard,, A. M. Heegaard,, N. Hélix,, M. Stahlhut,, M. C. Ovejero,, J. V. Johansen,, H. Solberg,, T. L. Andersen,, D. Hougaard,, M. Berryman,, C. B. Shiødt,, B. H. Sørensen,, J. Lichtenberg,, P. Christophersen,, N. T. Foged,, J. M. Delaissé,, M. T. Engsig,, and M. A. Karsdal. 2004. The chloride channel inhibitor n53736 prevents bone resorption in ovariectomized rats without changing bone formation. J. Bone Miner. Res. 19:11441153.
137. Schmidt-Rose, T.,, and T. J. Jentsch. 1997a. Transmembrane topology of a CLC chloride channel. Proc. Natl. Acad. Sci. USA 94:76337638.
138. Schmidt-Rose, T.,, and T. J. Jentsch. 1997b. Reconstitution of functional voltage-gated chloride channels from complementary fragments of CLC-1. J. Biol. Chem. 272:2051520521.
139. Schwake, M.,, T. Friedrich,, and T. J. Jentsch. 2001. An internalization signal in ClC-5, an endosomal Cl− channel mutated in Dent’s disease. J. Biol. Chem. 276:1204912054.
140. Schwappach, B.,, S. Stobrawa,, M. Hechenberger,, K. Steinmeyer,, and T. J. Jentsch. 1998. Golgi localization and functionally important domains in the NH2 and COOH terminus of the yeast CLC putative chloride channel Gef1p. J. Biol. Chem. 273:1511015118.
141. Scott, J. W.,, S. A. Hawley,, K. A. Green,, M. Anis,, G. Stewart,, G. A. Scullion,, D. G. Norman,, and D. G. Hardie. 2004. CBS domains form energy-sensing modules whose binding of adenosine ligands is disrupted by disease mutations. J. Clin. Investig. 113:274284.
142. Sheng, M.,, and E. Kim. 2000. The Shank family of scaffold proteins. J. Cell Sci. 113(Part 11):18511856.
143. Simon, D. B.,, R. S. Bindra,, T. A. Mansfield,, C. Nelson-Williams,, E. Mendonca,, R. Stone,, S. Schurman,, A. Nayir,, H. Alpay,, A. Bakkaloglu,, J. Rodriguez-Soriano,, J. M. Morales,, S. A. Sanjad,, C. M. Taylor,, D. Pilz,, A. Brem,, H. Trachtman,, W. Griswold,, G. A. Richard,, E. John,, and R. P. Lifton. 1997. Mutations in the chloride channel gene, CLCNKB, cause Bartter’s syndrome type III. Nat. Genet. 17:171178.
144. Simpson, B. J.,, T. A. Height,, G. Y. Rychkov,, K. J. Nowak,, N. G. Laing,, B. P. Hughes,, and A. H. Bretag. 2004. Characterization of three myotonia-associated mutations of the CLCN1 chloride channel gene via heterologous expression. Hum. Mutat. MIB 24:185.
145. Steinmeyer, K.,, R. Klocke,, C. Ortland,, M. Gronemeier,, H. Jockusch,, S. Gründer,, and T. J. Jentsch. 1991a. Inactivation of muscle chloride channel by transposon insertion in myotonic mice. Nature 354: 304308.
146. Steinmeyer, K.,, C. Ortland,, and T. J. Jentsch. 1991b. Primary structure and functional expression of a developmentally regulated skeletal muscle chloride channel. Nature 354:301304.
147. Steinmeyer, K.,, B. Schwappach,, M. Bens,, A. Vandewalle,, and T. J. Jentsch. 1995. Cloning and functional expression of rat CLC-5, a chloride channel related to kidney disease. J. Biol. Chem. 270:3117231177.
148. Stobrawa, S. M.,, T. Breiderhoff,, S. Takamori,, D. Engel,, M. Schweizer,, A. A. Zdebik,, M. R. Bösl,, K. Ruether,, H. Jahn,, A. Draguhn,, R. Jahn,, and T. J. Jentsch. 2001. Disruption of ClC-3, a chloride channel expressed on synaptic vesicles, leads to a loss of the hippocampus. Neuron 29:185196.
149. Stroffekova, K.,, E. Y. Kupert,, D. H. Malinowska,, and J. Cuppoletti. 1998. Identification of the pH sensor and activation by chemical modification of the ClC-2G Cl- channel. Am. J. Physiol. 275:C1113C1123.
150. Thevenod, F. 2002. Ion channels in secretory granules of the pancreas and their role in exocytosis and release of secretory proteins. Am. J. Physiol. Cell Physiol. 283:C651C672.
151. Thiemann, A.,, S. Gründer,, M. Pusch,, and T. J. Jentsch. 1992. A chloride channel widely expressed in epithelial and non-epithelial cells. Nature 356:5760.
152. Tieleman, D. P.,, I. H. Shrivastava,, M. R. Ulmschneider,, and M. S. Sansom. 2001. Proline-induced hinges in transmembrane helices: possible roles in ion channel gating. Proteins 44:6372.
153. Uchida, S. 2000. In vivo role of CLC chloride channels in the kidney. Am. J. Physiol. Renal Physiol. 279:F802F808.
154. Uchida, S.,, S. Sasaki,, T. Furukawa,, M. Hiraoka,, T. Imai,, Y. Hirata,, and F. Marumo. 1993. Molecular cloning of a chloride channel that is regulated by dehydration and expressed predominantly in kidney medulla. J. Biol. Chem. 268:38213824.
155. Uchida, S.,, Y. Tanaka,, H. Ito,, F. Saitoh-Ohara,, J. Inazawa,, K. K. Yokoyama,, S. Sasaki,, and F. Marumo. 2000. Transcriptional regulation of the CLC-K1 promoter by myc-associated zinc finger protein and kidneyenriched Krüppel-like factor, a novel zinc finger repressor. Mol. Cell Biol. 20:73197331.
156. Valverde, M. A.,, S. P. Hardy,, and F. V. Sepulveda. 1995. Chloride channels: a state of flux. FASEB J. 9:509515.
157. Vanoye, C. G.,, and A. L. George, Jr. 2002. Functional characterization of recombinant human ClC-4 chloride channels in cultured mammalian cells. J. Physiol. 539:373383.
158. van Slegtenhorst, M. A.,, M. T. Bassi,, G. Borsani,, M. C. Wapenaar,, G. B. Ferrero,, L. de Conciliis,, E. I. Rugarli,, A. Grillo,, B. Franco,, H. Y. Zoghbi, et al. 1994. A gene from the Xp22.3 region shares homology with voltage-gated chloride channels. Hum. Mol. Genet. 3:547552.
159. Varela, D.,, M. I. Niemeyer,, L. P. Cid,, and F. V. Sepulveda. 2002. Effect of an N-terminus deletion on voltagedependent gating of the ClC-2 chloride channel. J. Physiol. 544:363372.
160. Wang, G. L.,, X. R. Wang,, M. J. Lin,, H. He,, X. J. Lan,, and Y. Y. Guan. 2002. Deficiency in ClC-3 chloride channels prevents rat aortic smooth muscle cell proliferation. Circ. Res. 91:E28E32.
161. Wang, G. X.,, W. J. Hatton,, G. L. Wang,, J. Zhong,, I. Yamboliev,, D. Duan,, and J. R. Hume. 2003. Functional effects of novel anti-ClC-3 antibodies on native volume-sensitive osmolyte and anion channels in cardiac and smooth muscle cells. Am. J. Physiol. Heart Circ. Physiol. 285:H1453H1463.
162. Warner, A. E. 1972. Kinetic properties of the chloride conductance of frog muscle. J. Physiol. 227:291312.
163. Weaver, A. M.,, M. E. Young,, W. L. Lee,, and J. A. Cooper. 2003. Integration of signals to the Arp2/3 complex. Curr. Opin. Cell Biol. 15:2330.
164. White, M. M.,, and C. Miller. 1979. A voltage-gated anion channel from the electric organ of Torpedo californica. J. Biol. Chem. 254:1016110166.
165. Yamazaki, J.,, D. Duan,, R. Janiak,, K. Kuenzli,, B. Horowitz,, and J. R. Hume. 1998. Functional and molecular expression of volume-regulated chloride channels in canine vascular smooth muscle cells. J. Physiol. 507:729736.
166. Yoshikawa, M.,, S. Uchida,, J. Ezaki,, T. Rai,, A. Hayama,, K. Kobayashi,, Y. Kida,, M. Noda,, M. Koike,, Y. Uchiyama,, F. Marumo,, E. Kominami,, and S. Sasaki. 2002. CLC-3 deficiency leads to phenotypes similar to human neuronal ceroid lipofuscinosis. Genes Cells 7:597605.
167. Zheng, Y. J.,, T. Furukawa,, T. Ogura,, K. Tajimi,, and N. Inagaki. 2002. M phase-specific expression and phosphorylation-dependent ubiquitination of the ClC-2 channel. J. Biol. Chem. 277:3226832273.


Generic image for table
Table 1.

CLC nomenclature

Citation: Rickards H, Bartley P, Bretag A, Bagley C. 2005. The CLC Family of Proteins: Chloride Transporters and Channels, p 209-246. In Kubalski A, Martinac B (ed), Bacterial Ion Channels and Their Eukaryotic Homologs. ASM Press, Washington, DC. doi: 10.1128/9781555816452.ch11

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