CaMKII Triggers the Diffusional Trapping of Surface AMPARs through Phosphorylation of Stargazin
CaMKII Triggers the Diffusional Trapping of Surface AMPARs through Phosphorylation of Stargazin
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DOI：
10.1016/j.neuron.2010.06.007
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发表时间：
2010-07-29
期刊：
影响因子：
16.2
通讯作者：
Choquet, Daniel
中科院分区：
文献类型：
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作者：
Opazo, Patricio;Labrecque, Simon;Choquet, Daniel
钙/钙调素依赖性蛋白激酶II（CaMKII）是AMPA型谷氨酸受体（AMPAR）在发育和可塑性过程中的突触募集所必需的。然而，其潜在机制尚不清楚。使用单粒子跟踪的AMPARs，我们表明，CaMKII激活和突触后易位诱导的AMPARs扩散在膜上的突触陷阱。AMPAR固定需要辅助亚基Stargazin的磷酸化及其与PDZ结构域支架的结合。它不依赖于GluA 1 AMPAR亚基的PDZ结合结构域，也不依赖于其Ser 831的磷酸化。最后，CaMKII依赖的AMPAR固定调节短期可塑性。因此，突触后NMDA依赖性Ca 2+内流触发了控制突触功能的突触处AMPAR扩散交换的CaMKII和Stargazin依赖性降低。
The Ca2+/calmodulin-dependent protein kinase II (CaMKII) is critically required for the synaptic recruitment of AMPA-type glutamate receptors (AMPARs) during both development and plasticity. However, the underlying mechanism is unknown. Using single-particle tracking of AMPARs, we show that CaMKII activation and postsynaptic translocation induce the synaptic trapping of AMPARs diffusing in the membrane. AMPAR immobilization requires both phosphorylation of the auxiliary subunit Stargazin and its binding to PDZ domain scaffolds. It does not depend on the PDZ binding domain of GluA1 AMPAR subunit nor its phosphorylation at Ser831. Finally, CaMKII-dependent AMPAR immobilization regulates short-term plasticity. Thus, NMDA-dependent Ca2+ influx in the post-synapse triggers a CaMKII- and Stargazin-dependent decrease in AMPAR diffusional exchange at synapses that controls synaptic function.