Specific Roles of AMPA Receptor Subunit GluR1 (GluA1) Phosphorylation Sites in Regulating Synaptic Plasticity in the CA1 Region of Hippocampus
Specific Roles of AMPA Receptor Subunit GluR1 (GluA1) Phosphorylation Sites in Regulating Synaptic Plasticity in the CA1 Region of Hippocampus
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DOI：
10.1152/jn.00835.2009
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发表时间：
2010-01-01
影响因子：
2.5
通讯作者：
Huganir, Richard L.
中科院分区：
文献类型：
--
作者：
Lee, Hey-Kyoung;Takamiya, Kogo;Huganir, Richard L.
Lee H-K，Takamiya K，He K，Song L，Huganir RL. AMPA受体亚单位GluR 1（GluA 1）磷酸化位点在调节海马CA 1区突触可塑性中的特殊作用。J Neurophysiol 103：479-489，2010.首次发表于2009年11月11日; doi：10.1152/jn.00835.2009。中枢神经系统兴奋性突触传递的活动依赖性变化依赖于α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPAR）的调节。特别是，一些证据表明AMPAR亚基谷氨酸受体1 GluR 1（也称为GluA 1或（GluR-A））的可逆磷酸化在长时程增强（LTP）和长时程抑制（LTD）中起作用。我们以前报道过丝氨酸（S）831和845对GluR 1亚基的调节可能在CA 1的Schaffer侧支输入的双向突触可塑性中起关键作用。具体而言，缺乏S831和S845磷酸化位点的基因敲入小鼠（“双磷酸突变体”），其中两个丝氨酸残基都被丙氨酸取代（A），显示出更快的LTP衰减和LTD缺陷。为了确定两个磷酸化位点中的哪一个是造成表型的原因，我们现在产生了两个基因敲入小鼠系：一种特异性缺乏S831（S831 A突变体），另一种仅缺乏S845（S845 A突变体）。我们发现，S831 A突变体显示正常的LTP和LTD，而S845 A突变体显示出特定的赤字在LTD。与我们以前的结果一起从“双磷酸突变体”，我们的数据表明，无论是S831或S845单独可以支持LTP，而S845网站是LTD的表达是至关重要的。
Lee H-K, Takamiya K, He K, Song L, Huganir RL. Specific roles of AMPA receptor subunit GluR1 (GluA1) phosphorylation sites in regulating synaptic plasticity in the CA1 region of hippocampus. J Neurophysiol 103: 479-489, 2010. First published November 11, 2009; doi: 10.1152/jn.00835.2009. Activity-dependent changes in excitatory synaptic transmission in the CNS have been shown to depend on the regulation of alpha-a mino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs). In particular, several lines of evidence suggest that reversible phosphorylation of AMPAR subunit glutamate receptor 1 GluR1, also referred to as GluA1 or (GluR-A) plays a role in long-term potentiation (LTP) and long-term depression LTD). We previously reported that regulation of serines (S) 831 and 845 on the GluR1 subunit may play a critical role in bidirectional synaptic plasticity in the Schaffer collateral inputs to CA1. Specifically, gene knockin mice lacking both S831 and S845 phosphorylation sites ("double phosphomutants"), where both serine residues were replaced by alanines (A), showed a faster decaying LTP and a deficit in LTD. To determine which of the two phosphorylation sites was responsible for the phenotype, we have now generated two lines of gene knockin mice: one that specifically lacks (S831 (S831A mutants) and another that lacks only S845 (S845A mutants). We found that S831A mutants display normal LTP and LTD, whereas S845A mutants show a specific deficit in LTD. Taken together with our previous results from the "double phosphomutants," our data suggest that either S831 or S845 alone may support LTP, whereas the S845 site is critical for LTD expression.