PKC phosphorylates GluA1-Ser831 to enhance AMPA receptor conductance
PKC phosphorylates GluA1-Ser831 to enhance AMPA receptor conductance
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DOI：
10.4161/chan.18648
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发表时间：
2012-01-01
期刊：
影响因子：
3.3
通讯作者：
Traynelis, Stephen F.
中科院分区：
文献类型：
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作者：
Jenkins, Meagan A.;Traynelis, Stephen F.
AMPA受体在大脑中介导快速兴奋性突触传递，并通过C末端结构域中多个残基的磷酸化来动态调节。CaMKII磷酸化AMPA受体GluA1亚基内的Ser831以增加单通道电导，生化研究表明PKC也可以磷酸化该残基。鉴于在GluA1 C末端发现了额外的PKC磷酸化位点，目前尚不清楚Ser831的PKC磷酸化是否增加了完整受体的GluA1电导。在这里，我们报道了纯化的PKC催化亚基显著增加了HEK293T细胞中在Stargazin存在下表达的野生型GluA1 AMPA受体的电导。此外，突变GluA1-S831A阻断了PKC的功能效应。这些发现表明，激活CaMKII或PKC可以增加GluA1 AMPA受体的电导，该位点的磷酸化提供了一种通过各种蛋白质信号级联来调节通道的机制。
AMPA receptors mediate fast excitatory synaptic transmission in the brain, and are dynamically regulated by phosphorylation of multiple residues within the C-terminal domain. CaMKII phosphorylates Ser831 within the AMPA receptor GluA1 subunit to increase single channel conductance, and biochemical studies show that PKC can also phosphorylate this residue. In light of the discovery of additional PKC phosphorylation sites within the GluA1 C-terminus, it remains unclear whether PKC phosphorylation of Ser831 increases GluA1 conductance in intact receptors. Here, we report that the purified, catalytic subunit of PKC significantly increases the conductance of wild-type GluA1 AMPA receptors expressed in the presence of stargazin in HEK293T cells. Furthermore, the mutation GluA1-S831A blocks the functional effect of PKC. These findings suggest that GluA1 AMPA receptor conductance can be increased by activated CaMKII or PKC, and that phosphorylation at this site provides a mechanism for channel modulation via a variety of protein signaling cascades.