Primary structure of Torpedo marmorata chloride channel isolated by expression cloning in Xenopus oocytes

Jentsch, Thomas J.; Steinmeyer, Klaus; Schwarz, Gert

doi:10.1038/348510a0

Cited by 491 publications

(274 citation statements)

References 45 publications

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“…The cloning of the ClC-0 gene (Jentsch et al 1990) led to the identification of a wide family of related proteins whose members are present in many bacteria and in all eukaryotic organisms analysed up to now (Miller 2006). There are nine members of the CLC family in humans.…”

Section: The Plant Clc Familymentioning

confidence: 99%

CLC-mediated anion transport in plant cells

Angeli

Monachello

Ephritikhine

et al. 2008

Phil. Trans. R. Soc. B

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Plants need nitrate for growth and store the major part of it in the central vacuole of cells from root and shoot tissues. Based on few studies on the two model plants Arabidopsis thaliana and rice, members of the large ChLoride Channel (CLC) family have been proposed to encode anion channels/transporters involved in nitrate homeostasis. Proteins from the Arabidopsis CLC family (AtClC, comprising seven members) are present in various membrane compartments including the vacuolar membrane (AtClCa), Golgi vesicles (AtClCd and AtClCf ) or chloroplast membranes (AtClCe). Through a combination of electrophysiological and genetic approaches, AtClCa was shown to function as a 2NO 3 K /1H C exchanger that is able to accumulate specifically nitrate into the vacuole, in agreement with the main phenotypic trait of knockout mutant plants that accumulate 50 per cent less nitrate than their wild-type counterparts. The set-up of a functional complementation assay relying on transient expression of AtClCa cDNA in the mutant background opens the way for studies on structure-function relationships of the AtClCa nitrate transporter. Such studies will reveal whether important structural determinants identified in bacterial or mammalian CLCs are also crucial for AtClCa transport activity and regulation.

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Section: The Plant Clc Familymentioning

confidence: 99%

CLC-mediated anion transport in plant cells

Angeli

Monachello

Ephritikhine

et al. 2008

Phil. Trans. R. Soc. B

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“…The founding member is the voltage-gated Cl channel CLC-0 that has been expression-cloned by Jentsch and colleagues [Jentsch et al, 1990]. CLC channels are found in all higher species and in most prokaryotes and can be can be classified into three groups based on sequence similarity .…”

Section: Clc-1 and The Clc Family Of CL Channelsmentioning

confidence: 99%

Myotonia caused by mutations in the muscle chloride channel geneCLCN1

2002

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Pure non-syndromic, non-dystrophic myotonia in humans is caused by mutations in the genes coding for the skeletal muscle sodium channel (SCN5A) or the skeletal muscle chloride channel (CLCN1) with similar phenotypes. Chloride-channel myotonia can be dominant (Thomsen-type myotonia) or recessive (Becker-type myotonia). More than 60 myotonia-causing mutations in the CLCN1 gene have been identified, with only a few of them being dominant. A common phenotype of dominant mutations is a dominant negative effect of mutant subunits in mutant-WT heterodimers, causing a large shift of the steady-state open probability voltage-dependence towards more positive, unphysiological voltages. The study of the properties of disease causing mutations has helped in understanding the functional properties of the CLC-1 channel that is part of a nine-member gene family of chloride channels. The large body of knowledge obtained for CLC-1 may also help to better understand the other CLC channels, three of which are also involved in genetic diseases.

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“…Ϫ channels represents the largest known gene family coding for anion channels (1)(2)(3). At least nine human isoforms (ClC-1 to ClC-7, ClC-Ka, and ClCKb) are expressed in various tissues and play important roles in the function of various organs.…”

Section: The Clc Family Of Voltage-gated CLmentioning

confidence: 99%

“…Human ClC-1 (hClC-1) 1 exhibits at least two functionally distinct ion binding sites within the pore (8,10), both preferring large and polyatomic anions over chloride. The tighter binding of these anions reduces their turnover, resulting in lower permeability and conductivity, thus making chloride the most permeant anion (8,9).…”

Section: The Clc Family Of Voltage-gated CLmentioning

confidence: 99%

Residues Lining the Inner Pore Vestibule of Human Muscle Chloride Channels

Fahlke¹,

Gillani²,

George³

2001

Journal of Biological Chemistry

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Chloride channels belonging to the ClC family are ubiquitous and participate in a wide variety of physiological and pathophysiological processes. To define sequence segments in ClC channels that contribute to the formation of their ion conduction pathway, we employed a combination of site-directed mutagenesis, heterologous expression, patch clamp recordings, and chemical modification of the human muscle ClC isoform, hClC-1. We demonstrate that a highly conserved 8-amino acid motif (P3) located in the linker between transmembrane domains D2 and D3 contributes to the formation of a wide pore vestibule facing the cell interior. Similar to a previously defined pore region (P1 region), this segment functionally interacts with the corresponding segment of the contralateral subunit. The use of cysteine-specific reagents of different size revealed marked differences in the diameter of pore-forming regions implying that ClC channels exhibit a pore architecture quite similar to that of certain cation channels, in which a narrow constriction containing major structural determinants of ion selectivity is neighbored by wide vestibules on both sides of the membrane. The ClC family of voltage-gated ClϪ channels represents the largest known gene family coding for anion channels (1-3). At least nine human isoforms (ClC-1 to ClC-7, ClC-Ka, and ClCKb) are expressed in various tissues and play important roles in the function of various organs. Mutations in the genes coding for three ClC isoforms cause inherited human diseases. CLCN1 represents the genetic locus for myotonia congenita (4, 5), a muscle disease characterized by stiffness upon sudden forceful movement. Mutations in CLCN5 cause Dent's disease, an inherited renal disorder associated with hypercalciuria, nephrolithiasis, and low molecular weight proteinuria (6). Genetic alterations of CLCNKB are responsible for type III Bartter's syndrome, a salt-wasting renal tubular disorder causing hypovolemia, hyponatremia, and hypotension (7).Heterologous expression of many cloned ClC isoforms have revealed highly anion-selective ion channels, and it is therefore reasonable to predict that evolutionarily conserved structures confer anion selectivity to their ion conduction pathways. Elucidating the molecular mechanisms responsible for ion selectivity and conduction in ClC channels is key to understanding the function and dysfunction of this important family of ion channels. Moreover, primary sequence information about the ionic pore represents the first step for a rationally designing compounds to block or open these ion channels that play important roles in human diseases.We recently probed the ion conduction pathway of human ClC-1 in the presence of several different permeant anions (8), and we demonstrated an unusual ion selectivity mechanism that depends upon differential ion binding to discriminate among anions (8, 9). Human ClC-1 (hClC-1) 1 exhibits at least two functionally distinct ion binding sites within the pore (8, 10), both preferring large and polyatomic anions over chl...

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Primary structure of Torpedo marmorata chloride channel isolated by expression cloning in Xenopus oocytes

Cited by 491 publications

References 45 publications

CLC-mediated anion transport in plant cells

CLC-mediated anion transport in plant cells

Myotonia caused by mutations in the muscle chloride channel geneCLCN1

Residues Lining the Inner Pore Vestibule of Human Muscle Chloride Channels

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