A novel regulatory locus of phosphorylation in the C terminus of the potassium chloride cotransporter KCC2 that interferes with N-ethylmaleimide or staurosporine-mediated activation.

ABSTRACT: The neuron-specific cation chloride cotransporter KCC2 plays a crucial role in hyperpolarizing synaptic inhibition. Transporter dysfunction is associated with various neurological disorders, raising interest in regulatory mechanisms. Phosphorylation has been identified as a key regulatory process. Here, we retrieved experimentally observed phosphorylation sites of KCC2 from public databases and report on the systematic analysis of six phosphorylated serines, Ser(25), Ser(26), Ser(937), Ser(1022), Ser(1025), and Ser(1026). Alanine or aspartate substitutions of these residues were analyzed in HEK-293 cells. All mutants were expressed in a pattern similar to wild-type KCC2 (KCC2(WT)). Tl(+) flux measurements demonstrated unchanged transport activity for Ser(25), Ser(26), Ser(1022), Ser(1025),

SUBMITTER: Weber M 

PROVIDER: S-EPMC4081912 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature