Regulation of NMDA Receptors by an Associated Phosphatase-Kinase Signaling Complex
Ryan S. Westphal,
1*
Steven J. Tavalin,
1*
Jerry W. Lin,
2
Neal M. Alto,
1
Iain
D. C. Fraser,
1
Lorene K. Langeberg,
1
Morgan Sheng,
2
John D. Scott
1
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.
1 Howard Hughes Medical Institute, Vollum
Institute, Oregon Health Sciences University, 3181 S.W. Sam Jackson
Road, Portland, OR 97201, USA.
2 Howard Hughes
Medical Institute and Department of Neurobiology, Massachusetts General
Hospital and Harvard Medical School, Boston, MA 02114, USA.
*
These authors contributed equally to this article.
To whom correspondence should be addressed. E-mail:
scott{at}ohsu.edu
