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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,
Synergism between halide binding and proton transport in a CLC-type exchanger.
2006, Pubmed
Accardi,
Synergism between halide binding and proton transport in a CLC-type exchanger.
2006,
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 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,
Gating the selectivity filter in ClC chloride channels.
2003,
Pubmed
,
Xenbase Dutzler,
X-ray structure of a ClC chloride channel at 3.0 A reveals the molecular basis of anion selectivity.
2002,
Pubmed 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 Jentsch,
CLC chloride channels and transporters: from genes to protein structure, pathology and physiology.
2008,
Pubmed 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 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 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,
Cloning and functional expression of rat CLC-5, a chloride channel related to kidney disease.
1995,
Pubmed
,
Xenbase Steinmeyer,
Inactivation of muscle chloride channel by transposon insertion in myotonic mice.
1991,
Pubmed von der Fecht-Bartenbach,
Function of the anion transporter AtCLC-d in the trans-Golgi network.
2007,
Pubmed 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,
Buffered diffusion around a spherical proton pumping cell: a theoretical analysis.
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 Zúñiga,
The voltage-dependent ClC-2 chloride channel has a dual gating mechanism.
2004,
Pubmed
