通过蛋白激酶A对谷氨酸受体1亚基的磷酸化作用调控α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体的转运
Regulation of {alpha}-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor trafficking through PKA phosphorylation of the Glu receptor 1 subunit.
作者信息
Man Heng-Ye, Sekine-Aizawa Yoko, Huganir Richard L
机构信息
Howard Hughes Medical Institute and Department of Neuroscience, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
出版信息
Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3579-84. doi: 10.1073/pnas.0611698104. Epub 2007 Feb 21.
Abstract
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.
摘要
α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体介导大脑中大部分兴奋性突触传递。最近的研究表明，蛋白激酶A（PKA）的激活调节AMPA受体谷氨酸受体1（GluR1）亚基的膜转运，但GluR1直接磷酸化在调节受体再分布中的作用尚不清楚。在此我们表明，PKA诱导的AMPA受体细胞表面表达增加需要PKA使GluR1亚基的丝氨酸845磷酸化，因为它促进受体插入并减少受体内吞作用。此外，GluR1丝氨酸845的去磷酸化触发N-甲基-D-天冬氨酸（NMDA）诱导的AMPA受体内化。这些发现强烈表明，PKA对GluR1直接磷酸化的动态变化在AMPA受体转运和突触可塑性的调节中至关重要。
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