| K-Cl Co-transporter type 1 (KCC1) | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| Symbol | KCl_Cotrans_1 | ||||||||
| Pfam | PF03522 | ||||||||
| InterPro | IPR018491 | ||||||||
| TCDB | 2.A.30 | ||||||||
| |||||||||
In molecular biology, theelectroneutral cation-Cl (electroneutralpotassium chloride cotransporter)family of proteins are a family ofsolute carrierproteins. This family includes the products of the Humangenes:SLC12A1,SLC12A1,SLC12A2,SLC12A3,SLC12A4,SLC12A5,SLC12A6,SLC12A7,SLC12A8 andSLC12A9.
The K-Cl co-transporter (KCC) mediates the coupled movement ofK+ andCl−ions across theplasma membrane of manyanimal cells. This transport is involved in the regulatory volume decrease in response to cell swelling inred blood cells, and has been proposed to play a role in the vectorial movement of Cl− acrosskidneyepithelia. The transport process involves one for one electroneutral movement of K+ together with Cl−, and, in all knownmammalian cells, the net movement is outward.[1]
The neuronal KCC subtype KCC2 is cell-volume insensitive and plays a unique role in maintaining low intracellular Cl−concentration, which is required inneurones for the functioning of Cl− dependent fastsynaptic inhibition, mediated by certainneurotransmitters, such asgamma-aminobutyric acid (GABA) andglycine.
Threeisoforms of the K-Cl co-transporter have been described, termedKCC1 (SLC12A4),KCC2 (SLC12A5), andKCC3 (SLC12A6), containing 1085, 1116 and 1150amino acids, respectively. They are predicted to have 12transmembrane (TM) regions in a central hydrophobic domain, together withhydrophilicN- andC-termini that are likelycytoplasmic. Comparison of theirsequences with those of other ion-transportingmembrane proteins reveals that they are part of a new superfamily ofcation-chloride co-transporters, which includes theNa-Cl and Na-K-2Cl co-transporters. KCC1 and KCC3 are widelyexpressed inhuman tissues, while KCC2 is expressed only inbrain neurons, making it likely that this is theisoform responsible for maintaining low Cl−concentration in neurons.[2][3][4] A study in the model organismC. elegans found that the KCC3 ortholog functions in glial cells to regulate animal behavior.[5]
KCC1 is widely expressed inhuman tissues, and when heterologously expressed, possesses the functional characteristics of the well-studied red blood cell K-Cl co-transporter, including stimulation by both swelling and N-ethylmaleimide. Severalsplice variants have also been identified.
KCC3 is widely expressed in humantissues and, like KCC1, is stimulated by both swelling andN-ethylmaleimide. The induction of KCC3 is up-regulated byvascular endothelial growth factor and down-regulated bytumour necrosis factor. Defects in KCC3 are linked toagenesis of thecorpus callosum withperipheral neuropathy.[6] This disorder is characterised by severe progressivesensorimotorneuropathy,mental retardation,dysmorphic features and complete or partial agenesis of the corpus callosum.