Icln, An Ion Channel‐Forming Protein Associated with Cell Volume Regulation

Gschwentner, Martin; Fürst, Johannes; Ritter, Markus; Bazzini, Claudia; Wöll, Ewald; Dienstl, Anton; Jakab, Martin; König, Matthias; Scandella, Elke; Rudzki, Jakob; Botta, Guido Fernando; Meyer, Gerd; Läng, Florian; Deetjen, P.; Paulmichl, Markus

doi:10.1111/j.1469-445x.1999.01941.x

Cited by 8 publications

(8 citation statements)

References 14 publications

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“…Mutations within this binding site rendered the channel insensitive to extracellularly applied nucleotides. Although suggestive of a potential channel function of ICln, these experiments cannot be taken as proof that ICln is indeed a channel (for a review see [20]). …”

mentioning

confidence: 99%

Structure and Function of the Ion Channel ICln

Fürst

Jakab

König

et al. 2000

Cell Physiol Biochem

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Normal function of organs and cells is tightly linked to the cytoarchitecture. Control of the cell volume is therefore vital for the organism. A widely established strategy of cells to counteract swelling is the activation of chloride and potassium channels, which leads to a net efflux of salt followed by water – a process termed regulatory volume decrease. Since there is evidence for swelling-dependent chloride channels (IClswell) being activated also during pathological processes, the identification of the molecular entity underlying IClswell is of utmost importance. Several proteins are discussed as the channel forming IClswell, i.e. phospholemman, p-glycoprotein, CLC-3 and ICln. In this review we would like to focus on the properties of ICln, a protein cloned from a m̲adin d̲arby c̲anine K̲idney (MDCK) cell library whose expression in Xenopus laevis oocytes resulted in a nucleotide sensitive outwardly rectifying chloride current closely resembling the biophysical properties of IClswell.

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confidence: 99%

Structure and Function of the Ion Channel ICln

Fürst

Jakab

König

et al. 2000

Cell Physiol Biochem

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“…Hypotonic shock activates regulatory volume decrease (RVD), by which cells re-establish their original volume by activating taurine, K + and Cl -efflux. The nucleotide-sensitive chloride current inducing protein ICln has been proposed as a player in RVD [6,7]. Heterologous expression of ICln in Xenopus laevis oocytes [8] or mammalian cells [9][10][11] is associated with an increase in chloride current that has similar biophysical features of the swelling-induced chloride current (ICl swell ).…”

Section: Introductionmentioning

confidence: 99%

EGF Stimulates ICl<sub>swell</sub> by a Redistribution of Proteins Involved in Cell Volume Regulation

Tamma

Dossena²,

Nofziger³

et al. 2011

Cell Physiol Biochem

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Background: ICln is a multifunctional protein involved in the generation of chloride currents activated during regulatory volume decrease (RVD) after cell swelling (ICl_swell). Growth factor receptors play a key role in different cellular processes and epidermal growth factor (EGF) regulates swelling-activated chloride permeability. Aim: We set out to investigate if the EGF-induced upregulation of ICl_swell could be explained by a rearrangement of ICln subcellular distribution and interaction with its molecular partners. Methods: NIH-3T3 fibroblasts were serum-deprived for 24 hours and stimulated with EGF (40 ng/ml) for 30 minutes. ICl_swell activation, ICln distribution and interaction with its molecular partner HSPC038 were assessed by whole cell patch clamp and fluorescence resonance energy transfer (FRET). Results: EGF treatment significantly enhanced the direct molecular interaction between ICln and HSPC038 and also resulted in an increase of ICln and HSPC038 association with the plasma membrane. Importantly, these events are associated with a significant increase of ICl_swell. Conclusions: The present data indicate that EGF might exert its role in the modulation of volume-sensitive chloride currents in part through activation and translocation of ICln and HSPC038 to the plasma membrane.

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“…Several proteins are thought to be molecular targets for SAC. The list of the candidates comprises ClC-2 (26), mdr-1 (27), phospholemman (28,29), ClC-3 (30), and ICln (4,31). Because the expression of these different proteins was done in cells bearing endogenous SAC, the experiments cannot unambiguously clarify whether these proteins are the channels responsible for the currents observed after cytoplasmic swelling.…”

Section: Discussionmentioning

confidence: 99%

“…This indicates that the ICln protein is critical to the appearance of the SAC current under hypotonic conditions. Based on experiments using immunohistochemistry and Western blots, we developed the hypothesis that ICln is a constitutively expressed protein that can be transposed from a water-soluble form in the cytosol into the membrane, thus leading to an ionic current (31). The fact that ICln can indeed act as an ion channel was confirmed by functionally reconstituting the protein into lipid bilayers (31,33).…”

Section: Discussionmentioning

confidence: 99%

“…Based on experiments using immunohistochemistry and Western blots, we developed the hypothesis that ICln is a constitutively expressed protein that can be transposed from a water-soluble form in the cytosol into the membrane, thus leading to an ionic current (31). The fact that ICln can indeed act as an ion channel was confirmed by functionally reconstituting the protein into lipid bilayers (31,33). In the absence of calcium, the current obtained in bilayers is more selective for cations than for anions; however, the addition of calcium shifts the selectivity toward chloride.…”

Section: Discussionmentioning

confidence: 99%

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The Promoter for Constitutive Expression of the Human ICln Gene CLNS1A

Scandella¹,

Nagl²,

Oehl³

et al. 2000

Journal of Biological Chemistry

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The ICln protein is expressed ubiquitously in mammals. Experiments designed to knock down the ICln protein in NIH 3T3 fibroblasts as well as in epithelial cells led to the conclusion that this protein is crucially involved in volume regulation after cytoplasmic swelling. Reconstitution of the ICln protein in lipid bilayers revealed the ion channel nature of ICln. Here we describe a new human promoter sequence, composed of 89 nucleotides, which is responsible for a highly constitutive expression of the ICln protein. The promoter sequence lacks a TATA box, and the transcription can be effected at multiple sites. In addition to the starting sites, upstream sequence elements are mandatory for an efficient transcription of the ICln gene (CLNS1A). These new nucleotide elements were defined by site-directed mutagenesis.

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Icln, An Ion Channel‐Forming Protein Associated with Cell Volume Regulation

Cited by 8 publications

References 14 publications

Structure and Function of the Ion Channel ICln

Structure and Function of the Ion Channel ICln

EGF Stimulates ICl<sub>swell</sub> by a Redistribution of Proteins Involved in Cell Volume Regulation

The Promoter for Constitutive Expression of the Human ICln Gene CLNS1A

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