Crossing the Chloride Channel: The Current and Potential Therapeutic Value of the Neuronal K⁺-Cl^- Cotransporter KCC2

Figure 3

Schematic representation of important regulatory phosphoresidues of the neuron-specific K–Cl cotransporter KCC2. The mouse KCC2 co-transporter consists of 12 membrane spanning predicted segments, an N-linked glycosylated extracellular domain between transmembrane domains 5 and 6. This is flanked by two cytoplasmic carboxy- and amino-terminal domains of 104 and 481 amino acids, respectively. Positions of phosphoresidues that are critical for functional regulation of KCC2, including tyrosine 903 (Y903), threonine 906 (T906), serine 940 (S940), threonine 1006 (T1006, this site is corresponding to Rat T1007), tyrosine 1087 (Y1087), and S932 and T1008 (regulated by KCC2 activators staurosporine and N-ethylmalemide (NEM)), are indicated. The Purple region denotes the KCC2 ‘ISO’ domain, required for hyperpolarizing GABAergic transmission.