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Science. 1999 Jul 2;285(5424):93-6.

Regulation of NMDA receptors by an associated phosphatase-kinase signaling complex.

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  • 1Howard Hughes Medical Institute, Vollum Institute, Oregon Health Sciences University, 3181 S.W. Sam Jackson Road, Portland, OR 97201, USA.


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.

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