Disease relevance of Clns1a

• We demonstrated previously that expression of rat pICln in Escherichia coli conferred a strong resistance to hypotonic stress [1].
• Fractionation of C6 glioma cells into plasma membrane- and cytoplasm-containing fractions demonstrated that approximately 90% of the recovered pICln was confined to the cytosol [2].

High impact information on Clns1a

• Expression in Xenopus oocytes of a novel protein, pICln, activated a chloride conductance [3].
• Monoclonal antibodies recognizing pICln blocked activation of a native hypotonicity-induced chloride conductance (ICl.swell) in Xenopus oocytes, suggesting that pICln may link actin-bound cytoskeletal elements to an unidentified volume-sensitive chloride channel [3].
• The interaction between this protein and pICln was verified several ways, including the extraction of several pICln clones from a cDNA library using the 72-kDa protein as a bait in a yeast two-hybrid screen [4].
• When added to the external medium bathing Sf9 cells, pICln inserted into the plasma membrane and increased cell cation permeability [5].
• Phosphorylation of pICln with casein kinase II or mutation of G54, G56, and G58 to alanine decreased channel open probability and 86Rb+ uptake [5].

Chemical compound and disease context of Clns1a

• Immunoprecipitation of pICln from 32P-orthophosphoric acid-labeled C6 glioma cells revealed that the protein is phosphorylated constitutively, primarily on serine residues [6].

Biological context of Clns1a

• Mutagenesis studies led to the proposal that pICln is a swelling-activated anion channel [2].
• Similarly, transfection of cells with a green fluorescent protein-labeled pICln construct failed to reveal any membrane localization of the protein [2].
• pICln is found ubiquitously in mammalian cells and is postulated to play a critical role in cell volume regulation [2].
• The pICln-associated kinase displayed broad substrate specificity and was inhibited in a concentration-dependent manner by heparin, zinc and 5,6-dichloro-1-beta-D-ribofuranosylbenose (DRB) [6].

Anatomical context of Clns1a

• We tested the anion channel hypothesis by reconstituting recombinant pICln into artificial and biological membranes [5].
• We report the cloning and sequencing from human reticulocytes of cDNA coding for the Cl- channel-associated protein, pICln [7].
• Human reticulocyte pICln (HRpICln) cDNA encodes a protein (predicted molecular mass 26293Da) identical with human non-pigmented ciliary epithelial cell pICln [7].
• Moreover the association of RBC pICln with actin offers a model in which to test interactions between RBC ion channels and the cytoskeleton [7].
• Human NPE cell lines exhibited significant levels of pICln transcripts [8].

Associations of Clns1a with chemical compounds

• Molecular characterization of a swelling-induced chloride conductance regulatory protein, pICln [3].
• Phosphopeptide mapping demonstrated that pICln contains at least two phosphorylated serine residues that are located on trypsin cleavage fragments rich in acidic amino acid residues [6].

Other interactions of Clns1a

• This study investigates changes in the messenger RNA (mRNA) expression levels of HCN2 and HCN4 encoding rat If channels; ClC-3, a candidate gene for swelling-activated Cl- channel, and pICln, a regulatory subunit of Cl- channels in rat hypertrophied heart induced by banding the abdominal aorta [9].

Analytical, diagnostic and therapeutic context of Clns1a

• To define the intramolecular functional domain responsible for the resistance, molecular dissection of pICln was performed and the obtained peptides were expressed in E. coli [1].
• Molecular cloning of the human volume-sensitive chloride conductance regulatory protein, pICln, from ocular ciliary epithelium [8].
• Immunofluorescence microscopy revealed that pICln is localized primarily, if not exclusively, to the cytoplasm of swollen and nonswollen cells [2].

References