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Residues important for nitrate/proton coupling in plant and mammalian CLC transporters.
Bergsdorf EY
,
Zdebik AA
,
Jentsch TJ
.
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Members of the CLC gene family either function as chloride channels or as anion/proton exchangers. The plant AtClC-a uses the pH gradient across the vacuolar membrane to accumulate the nutrient NO(3)(-) in this organelle. When AtClC-a was expressed in Xenopus oocytes, it mediated NO(3)(-)/H(+) exchange and less efficiently mediated Cl(-)/H(+) exchange. Mutating the "gating glutamate" Glu-203 to alanine resulted in an uncoupled anion conductance that was larger for Cl(-) than NO(3)(-). Replacing the "proton glutamate" Glu-270 by alanine abolished currents. These could be restored by the uncoupling E203A mutation. Whereas mammalian endosomal ClC-4 and ClC-5 mediate stoichiometrically coupled 2Cl(-)/H(+) exchange, their NO(3)(-) transport is largely uncoupled from protons. By contrast, the AtClC-a-mediated NO(3)(-) accumulation in plant vacuoles requires tight NO(3)(-)/H(+) coupling. Comparison of AtClC-a and ClC-5 sequences identified a proline in AtClC-a that is replaced by serine in all mammalian CLC isoforms. When this proline was mutated to serine (P160S), Cl(-)/H(+) exchange of AtClC-a proceeded as efficiently as NO(3)(-)/H(+) exchange, suggesting a role of this residue in NO(3)(-)/H(+) exchange. Indeed, when the corresponding serine of ClC-5 was replaced by proline, this Cl(-)/H(+) exchanger gained efficient NO(3)(-)/H(+) coupling. When inserted into the model Torpedo chloride channel ClC-0, the equivalent mutation increased nitrate relative to chloride conductance. Hence, proline in the CLC pore signature sequence is important for NO(3)(-)/H(+) exchange and NO(3)(-) conductance both in plants and mammals. Gating and proton glutamates play similar roles in bacterial, plant, and mammalian CLC anion/proton exchangers.
Accardi,
Separate ion pathways in a Cl-/H+ exchanger.
2005, Pubmed
Accardi,
Separate ion pathways in a Cl-/H+ exchanger.
2005,
Pubmed
Accardi,
Secondary active transport mediated by a prokaryotic homologue of ClC Cl- channels.
2004,
Pubmed
Accardi,
Synergism between halide binding and proton transport in a CLC-type exchanger.
2006,
Pubmed
Bösl,
Male germ cells and photoreceptors, both dependent on close cell-cell interactions, degenerate upon ClC-2 Cl(-) channel disruption.
2001,
Pubmed
De Angeli,
The nitrate/proton antiporter AtCLCa mediates nitrate accumulation in plant vacuoles.
2006,
Pubmed
De Angeli,
Review. CLC-mediated anion transport in plant cells.
2009,
Pubmed
Dutzler,
X-ray structure of a ClC chloride channel at 3.0 A reveals the molecular basis of anion selectivity.
2002,
Pubmed
Dutzler,
Gating the selectivity filter in ClC chloride channels.
2003,
Pubmed
,
Xenbase
Estévez,
Barttin is a Cl- channel beta-subunit crucial for renal Cl- reabsorption and inner ear K+ secretion.
2001,
Pubmed
,
Xenbase
Friedrich,
Mutational analysis demonstrates that ClC-4 and ClC-5 directly mediate plasma membrane currents.
1999,
Pubmed
,
Xenbase
Gaxiola,
The yeast CLC chloride channel functions in cation homeostasis.
1998,
Pubmed
Geelen,
Disruption of putative anion channel gene AtCLC-a in Arabidopsis suggests a role in the regulation of nitrate content.
2000,
Pubmed
Greene,
The GEF1 gene of Saccharomyces cerevisiae encodes an integral membrane protein; mutations in which have effects on respiration and iron-limited growth.
1993,
Pubmed
Gründer,
Regions involved in the opening of CIC-2 chloride channel by voltage and cell volume.
,
Pubmed
,
Xenbase
Hechenberger,
A family of putative chloride channels from Arabidopsis and functional complementation of a yeast strain with a CLC gene disruption.
1996,
Pubmed
,
Xenbase
Jentsch,
Primary structure of Torpedo marmorata chloride channel isolated by expression cloning in Xenopus oocytes.
1990,
Pubmed
,
Xenbase
Jentsch,
Chloride and the endosomal-lysosomal pathway: emerging roles of CLC chloride transporters.
2007,
Pubmed
Jentsch,
CLC chloride channels and transporters: from genes to protein structure, pathology and physiology.
2008,
Pubmed
Kasper,
Loss of the chloride channel ClC-7 leads to lysosomal storage disease and neurodegeneration.
2005,
Pubmed
Kornak,
Loss of the ClC-7 chloride channel leads to osteopetrosis in mice and man.
2001,
Pubmed
Lange,
ClC-7 requires Ostm1 as a beta-subunit to support bone resorption and lysosomal function.
2006,
Pubmed
Li,
The ClC-3 chloride channel promotes acidification of lysosomes in CHO-K1 and Huh-7 cells.
2002,
Pubmed
Lim,
Intracellular proton-transfer mutants in a CLC Cl-/H+ exchanger.
2009,
Pubmed
Lorenz,
Heteromultimeric CLC chloride channels with novel properties.
1996,
Pubmed
,
Xenbase
Ludewig,
Two physically distinct pores in the dimeric ClC-0 chloride channel.
1996,
Pubmed
,
Xenbase
Lurin,
Cloning and functional expression of a plant voltage-dependent chloride channel.
1996,
Pubmed
,
Xenbase
Marmagne,
Two members of the Arabidopsis CLC (chloride channel) family, AtCLCe and AtCLCf, are associated with thylakoid and Golgi membranes, respectively.
2007,
Pubmed
Matsumura,
Overt nephrogenic diabetes insipidus in mice lacking the CLC-K1 chloride channel.
1999,
Pubmed
Middleton,
Homodimeric architecture of a ClC-type chloride ion channel.
1996,
Pubmed
Miller,
A provisional transport mechanism for a chloride channel-type Cl-/H+ exchanger.
2009,
Pubmed
Nguitragool,
Uncoupling of a CLC Cl-/H+ exchange transporter by polyatomic anions.
2006,
Pubmed
Picollo,
Chloride/proton antiporter activity of mammalian CLC proteins ClC-4 and ClC-5.
2005,
Pubmed
Piwon,
ClC-5 Cl- -channel disruption impairs endocytosis in a mouse model for Dent's disease.
2000,
Pubmed
Pusch,
Gating of the voltage-dependent chloride channel CIC-0 by the permeant anion.
1995,
Pubmed
,
Xenbase
Rickheit,
Endocochlear potential depends on Cl- channels: mechanism underlying deafness in Bartter syndrome IV.
2008,
Pubmed
Scheel,
Voltage-dependent electrogenic chloride/proton exchange by endosomal CLC proteins.
2005,
Pubmed
,
Xenbase
Simon,
Mutations in the chloride channel gene, CLCNKB, cause Bartter's syndrome type III.
1997,
Pubmed
Steinmeyer,
Inactivation of muscle chloride channel by transposon insertion in myotonic mice.
1991,
Pubmed
Steinmeyer,
Cloning and functional expression of rat CLC-5, a chloride channel related to kidney disease.
1995,
Pubmed
,
Xenbase
Weinreich,
Pores formed by single subunits in mixed dimers of different CLC chloride channels.
2001,
Pubmed
Zdebik,
Determinants of anion-proton coupling in mammalian endosomal CLC proteins.
2008,
Pubmed
Zifarelli,
Conversion of the 2 Cl(-)/1 H+ antiporter ClC-5 in a NO3(-)/H+ antiporter by a single point mutation.
2009,
Pubmed
,
Xenbase
Zifarelli,
Buffered diffusion around a spherical proton pumping cell: a theoretical analysis.
2008,
Pubmed
Zúñiga,
The voltage-dependent ClC-2 chloride channel has a dual gating mechanism.
2004,
Pubmed
von der Fecht-Bartenbach,
Function of the anion transporter AtCLC-d in the trans-Golgi network.
2007,
Pubmed
