Post-translational modification biology of glutamate receptors and drug addiction.
Post-translational modification biology of glutamate receptors and drug addiction.
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DOI：
10.3389/fnana.2011.00019
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发表时间：
2011
影响因子：
2.9
通讯作者：
Wang JQ
中科院分区：
文献类型：
--
作者：
Mao LM;Guo ML;Jin DZ;Fibuch EE;Choe ES;Wang JQ
谷氨酸受体的翻译后共价修饰仍然是一个热门话题。早期的研究已经证实，这一受体家族，包括几乎所有的离子型和代谢型谷氨酸受体亚型，在其胞内区的丝氨酸、苏氨酸或酪氨酸残基上经历了主动的磷酸化。最近的证据表明，几种谷氨酸受体亚型是半胱氨酸残基棕榈酰化的直接底物。某些谷氨酸受体也会发生其他修饰，如泛素化和赖氨酸残基上的苏莫化。这些修饰在本质上是动态的和可逆的，可以通过改变突触输入来调节。受调控的修饰在许多方面显著影响受体，包括生化(合成、亚单位组装和蛋白质-蛋白质相互作用)、亚细胞重新分布(运输、内吞、突触递送和聚集)和生理方面的相互关联的变化，通常与突触可塑性的变化有关。谷氨酸受体在纹状体中丰富，并与多巴胺密切合作，调节纹状体信号。新的证据表明，纹状体谷氨酸受体的修饰过程对成瘾药物敏感，如精神刺激剂(可卡因和苯丙胺)。改变的修饰被认为与持久的受体/突触可塑性和药物寻找直接相关。本文综述了谷氨酸受体的几种主要修饰类型，并分析了这些修饰在纹状体信号和精神刺激剂成瘾发病机制中的作用。
Post-translational covalent modifications of glutamate receptors remain a hot topic. Early studies have established that this family of receptors, including almost all ionotropic and metabotropic glutamate receptor subtypes, undergoes active phosphorylation at serine, threonine, or tyrosine residues in their intracellular domains. Recent evidence identifies several glutamate receptor subtypes to be direct substrates for palmitoylation at cysteine residues. Other modifications such as ubiquitination and sumoylation at lysine residues also occur to certain glutamate receptors. These modifications are dynamic and reversible in nature and are regulatable by changing synaptic inputs. The regulated modifications significantly impact the receptor in many ways, including interrelated changes in biochemistry (synthesis, subunit assembling, and protein–protein interactions), subcellular redistribution (trafficking, endocytosis, synaptic delivery, and clustering), and physiology, usually associated with changes in synaptic plasticity. Glutamate receptors are enriched in the striatum and cooperate closely with dopamine to regulate striatal signaling. Emerging evidence shows that modification processes of striatal glutamate receptors are sensitive to addictive drugs, such as psychostimulants (cocaine and amphetamine). Altered modifications are believed to be directly linked to enduring receptor/synaptic plasticity and drug-seeking. This review summarizes several major types of modifications of glutamate receptors and analyzes the role of these modifications in striatal signaling and in the pathogenesis of psychostimulant addiction.