TY - JOUR
T1 - Postsynaptic density protein-95 regulates NMDA channel gating and surface expression
AU - Lin, Ying
AU - Skeberdis, V. Arvydas
AU - Francesconi, Anna
AU - Bennett, Michael V.L.
AU - Zukin, R. Suzanne
PY - 2004/11/10
Y1 - 2004/11/10
N2 - NMDA receptors (NMDARs) colocalize with postsynaptic density protein-95 (PSD-95), a multivalent synaptic scaffolding protein and core component of the postsynaptic density, at excitatory synapses. Although much is known about the identity and properties of scaffolding proteins, little is known about their actions on NMDAR function. Here we show that association of PSD-95 with NMDARs modulates channel gating and surface expression. PSD-95 increases the number of functional channels at the cell surface and channel opening rate of NMDARs, with little or no change in conductance, reversal potential, or mean open time. We show further that PSD-95 increases NMDAR surface expression by increasing the rate of channel insertion and decreasing the rate of channel internalization. The PDZ (PSD-95, discs large, zona occludens-1) binding motif at the distal end of the NR2 C-terminal tail is critical to the actions of PSD-95 on NMDAR function and surface expression. Given that activity bi-directionally modifies synaptic levels of PSD-95, our findings suggest a novel mechanism for activity-dependent regulation of NMDARs at central synapses.
AB - NMDA receptors (NMDARs) colocalize with postsynaptic density protein-95 (PSD-95), a multivalent synaptic scaffolding protein and core component of the postsynaptic density, at excitatory synapses. Although much is known about the identity and properties of scaffolding proteins, little is known about their actions on NMDAR function. Here we show that association of PSD-95 with NMDARs modulates channel gating and surface expression. PSD-95 increases the number of functional channels at the cell surface and channel opening rate of NMDARs, with little or no change in conductance, reversal potential, or mean open time. We show further that PSD-95 increases NMDAR surface expression by increasing the rate of channel insertion and decreasing the rate of channel internalization. The PDZ (PSD-95, discs large, zona occludens-1) binding motif at the distal end of the NR2 C-terminal tail is critical to the actions of PSD-95 on NMDAR function and surface expression. Given that activity bi-directionally modifies synaptic levels of PSD-95, our findings suggest a novel mechanism for activity-dependent regulation of NMDARs at central synapses.
KW - Channel gating
KW - Excitatory synapses
KW - NMDA receptors
KW - PDZ proteins
KW - PSD-95
KW - Receptor trafficking
KW - SAP-90
KW - Scaffolding proteins
KW - Zona occludens family of proteins
UR - http://www.scopus.com/inward/record.url?scp=8544244897&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=8544244897&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.3159-04.2004
DO - 10.1523/JNEUROSCI.3159-04.2004
M3 - Article
C2 - 15537884
AN - SCOPUS:8544244897
SN - 0270-6474
VL - 24
SP - 10138
EP - 10148
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 45
ER -