Regulation of NMDA receptors by an associated phosphatase-kinase signalingcomplex

Regulation of N-methyl-D-aspartate (NMDA) receptor activity by kinases and phosphatases contributes to the modulation of synaptic transmission. Target ing of these enzymes near the substrate is proposed to enhance phosphorylat ion-dependent modulation. Yotiao, an NMDA receptor-associated protein, boun d the type I protein phosphatase (PP1) and the adenosine 3',5'-monophosphat e (cAMP)-dependent protein kinase (PKA) holoenzyme. Anchored PP1 was active , limiting channel activity, whereas PKA activation overcame constitutive P P1 activity and conferred rapid enhancement of NMDA receptor currents. Henc e, yotiao is a scaffold protein that physically attaches PP1 and PKA to NMD A receptors to regulate channel activity.