Fig. 4.

Schematic model detailing the postulated mechanism whereby γ-adducin could stimulate NCC activity. This model is speculative at current. Since γ-adducin is not a kinase, it may act as a scaffold by anchoring a kinase (potentially SPAK or OSR1) to the dephosphorylated cotransporter (step 1). The anchored kinase phosphorylates NCC, which leads to an increase in transport activity (step 2). γ-Adducin dissociates from NCC after the kinase phosphorylates the cotrasporter (step 3). Dephosphorylation of NCC by the PP4 protein reduces NCC activity (step 4). The cycle can be repeated after the cotransporter has been dephosphorylated