TY - JOUR
T1 - Rapid Dispersion of SynGAP from Synaptic Spines Triggers AMPA Receptor Insertion and Spine Enlargement during LTP
AU - Araki, Yoichi
AU - Zeng, Menglong
AU - Zhang, Mingjie
AU - Huganir, Richard L.
PY - 2015/1/7
Y1 - 2015/1/7
N2 - SynGAP is a Ras-GTPase activating protein highly enriched at excitatory synapses in the brain. Previous studies have shown that CaMKII and the RAS-ERK pathway are critical for several forms of synaptic plasticity including LTP. NMDA receptor-dependent calcium influx has been shown to regulate the RAS-ERK pathway and downstream events that result inAMPA receptor synaptic accumulation, spine enlargement, and synaptic strengthening during LTP. However, the cellular mechanisms whereby calcium influx and CaMKII control Ras activity remain elusive. Using live-imaging techniques, we have found that SynGAP is rapidly dispersed from spines upon LTP induction in hippocampal neurons, and this dispersion depends on phosphorylation of SynGAP by CaMKII. Moreover, the degree of acute dispersion predicts the maintenance of spine enlargement. Thus, the synaptic dispersion of SynGAP by CaMKII phosphorylation during LTP represents a key signaling component that transduces CaMKII activity to small G protein-mediated spine enlargement, AMPA receptor synaptic incorporation, and synaptic potentiation.
AB - SynGAP is a Ras-GTPase activating protein highly enriched at excitatory synapses in the brain. Previous studies have shown that CaMKII and the RAS-ERK pathway are critical for several forms of synaptic plasticity including LTP. NMDA receptor-dependent calcium influx has been shown to regulate the RAS-ERK pathway and downstream events that result inAMPA receptor synaptic accumulation, spine enlargement, and synaptic strengthening during LTP. However, the cellular mechanisms whereby calcium influx and CaMKII control Ras activity remain elusive. Using live-imaging techniques, we have found that SynGAP is rapidly dispersed from spines upon LTP induction in hippocampal neurons, and this dispersion depends on phosphorylation of SynGAP by CaMKII. Moreover, the degree of acute dispersion predicts the maintenance of spine enlargement. Thus, the synaptic dispersion of SynGAP by CaMKII phosphorylation during LTP represents a key signaling component that transduces CaMKII activity to small G protein-mediated spine enlargement, AMPA receptor synaptic incorporation, and synaptic potentiation.
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U2 - 10.1016/j.neuron.2014.12.023
DO - 10.1016/j.neuron.2014.12.023
M3 - Article
C2 - 25569349
AN - SCOPUS:84920715741
VL - 85
SP - 173
EP - 189
JO - Neuron
JF - Neuron
SN - 0896-6273
IS - 1
ER -