Regulation of {alpha}-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor trafficking through PKA phosphorylation of the Glu receptor 1 subunit.
Regulation of {alpha}-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor trafficking through PKA phosphorylation of the Glu receptor 1 subunit.
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DOI：
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发表时间：
2007
影响因子：
11.1
通讯作者：
H. Man;Y. Sekine‐Aizawa;R. Huganir
中科院分区：
文献类型：
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作者：
H. Man;Y. Sekine‐Aizawa;R. Huganir
α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体介导脑中大部分兴奋性突触传递。最近的研究表明，PKA的活化调节AMPA受体Glu受体1（GluR 1）亚基的膜运输，但GluR 1的直接磷酸化在调节受体再分布中的作用尚不清楚。在这里，我们表明，磷酸化的GluR 1亚基丝氨酸845 PKA所需的PKA诱导的AMPA受体细胞表面表达的增加，因为它促进受体插入和减少受体内吞。此外，GluR 1丝氨酸845的去磷酸化触发NMDA诱导的AMPA受体内化。这些研究结果强烈表明，动态变化的直接磷酸化的GluR 1 PKA的AMPA受体运输和突触可塑性的调制是至关重要的。
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors mediate the majority of excitatory synaptic transmission in the brain. Recent studies have shown that activation of PKA regulates the membrane trafficking of the AMPA receptor Glu receptor 1 (GluR1) subunit, but the role of direct phosphorylation of GluR1 in regulating receptor redistribution is not clear. Here we show that phosphorylation of the GluR1 subunit on serine 845 by PKA is required for PKA-induced increases in AMPA receptor cell-surface expression because it promotes receptor insertion and decreases receptor endocytosis. Furthermore, dephosphorylation of GluR1 serine 845 triggers NMDA-induced AMPA receptor internalization. These findings strongly suggest that dynamic changes in direct phosphorylation of GluR1 by PKA are crucial in the modulation of AMPA receptor trafficking and synaptic plasticity.