Phosphorylation of AMPA receptors
Phosphorylation of AMPA receptors
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DOI：
10.1385/mn:32:3:237
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发表时间：
2005-12-01
影响因子：
5.1
通讯作者：
Mao, LM
中科院分区：
文献类型：
--
作者：
Wang, JQ;Arora, A;Mao, LM
离子型alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic酸(AMPA)受体广泛分布于哺乳动物脑内，主要参与介导快速兴奋性突触传递。最近在异源表达系统和培养的神经元中的研究表明，AMPA受体可以在其亚单位(GluR1、GluR2和GluR4)上被磷酸化。所有的磷酸化位点都位于细胞内C-末端的丝氨酸、苏氨酸或酪氨酸。几种关键的蛋白激酶，如蛋白激酶A、蛋白激酶C、钙/钙调蛋白依赖的蛋白激酶II和酪氨酸激酶(Trks；受体或非受体家族Trks)参与AMPA受体磷酸化的位点特异性调节。其他谷氨酸受体(N-甲基-D-天冬氨酸受体和代谢型谷氨酸受体)也通过蛋白质磷酸化机制调节AMPA受体。新的证据表明，作为一种快速和短期的机制，动态蛋白磷酸化直接调节AMPA受体的电生理、形态(外化和内化运输和聚集)和生化(合成和亚基组成)特性，以及AMPA受体亚基和各种细胞内相互作用蛋白之间的蛋白质相互作用。这些调节是最终影响多种形式突触可塑性的主要分子机制的基础。
The ionotropic alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor is densely distributed in the mammalian brain and is primarily involved in mediating fast excitatory synaptic transmission. Recent studies in both heterologous expression systems and cultured neurons have shown that the AMPA receptor can be phosphorylated on their subunits (GluR1, GluR2, and GluR4). All phosphorylation sites reside at serine, threonine, or tyrosine on the intracellular C-terminal domain. Several key protein kinases, such as protein kinase A, protein kinase C, Ca2+/calmodulin-dependent protein kinase II, and tyrosine kinases (Trks; receptor or nonreceptor family Trks) are involved in the site-specific regulation of the AMPA receptor phosphorylation. Other glutamate receptors (N-methyl-D-aspartate receptors and metabotropic glutamate receptors) also regulate AMPA receptors through a protein phosphorylation mechanism. Emerging evidence shows that as a rapid and short-term mechanism, the dynamic protein phosphorylation directly modulates the electrophysiological, morphological (externalization and internalization trafficking and clustering), and biochemical (synthesis and subunit composition) properties of the AMPA receptor, as well as protein-protein interactions between the AMPA receptor subunits and various intracellular interacting proteins. These modulations underlie the major molecular mechanisms that ultimately affect many forms of synaptic plasticity.