Regulation of NMDA Receptors by an Associated Phosphatase-Kinase Signaling Complex

Abstract

Regulation of N -methyl- d -aspartate (NMDA) receptor activity by kinases and phosphatases contributes to the modulation of synaptic transmission. Targeting of these enzymes near the substrate is proposed to enhance phosphorylation-dependent modulation. Yotiao, an NMDA receptor–associated protein, bound the type I protein phosphatase (PP1) and the adenosine 3′,5′-monophosphate (cAMP)–dependent protein kinase (PKA) holoenzyme. Anchored PP1 was active, limiting channel activity, whereas PKA activation overcame constitutive PP1 activity and conferred rapid enhancement of NMDA receptor currents. Hence, yotiao is a scaffold protein that physically attaches PP1 and PKA to NMDA receptors to regulate channel activity.