Department of Basic Medical Science, School of Medicine, University of Missouri-Kansas City Kansas City, MO, USA.
Front Neuroanat. 2011 Mar 17;5:19. doi: 10.3389/fnana.2011.00019. eCollection 2011.
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.
谷氨酸受体的翻译后共价修饰仍然是一个热门话题。早期的研究已经确定，该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，其细胞内结构域中的丝氨酸、苏氨酸或酪氨酸残基会发生活性磷酸化。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。其他修饰，如赖氨酸残基的泛素化和 sumoylation，也会发生在某些谷氨酸受体上。这些修饰是动态和可逆的，并且可以通过改变突触输入进行调节。受调节的修饰会以多种方式显著影响受体，包括生物化学（合成、亚基组装和蛋白质-蛋白质相互作用）、亚细胞重新分布（运输、内吞、突触传递和聚类）和生理学（通常与突触可塑性变化相关）的相互关联的变化。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。新出现的证据表明，纹状体谷氨酸受体的修饰过程对成瘾药物（如兴奋剂）敏感。改变的修饰被认为与持久的受体/突触可塑性和觅药直接相关。这篇综述总结了几种主要类型的谷氨酸受体修饰，并分析了这些修饰在纹状体信号传递和兴奋剂成瘾发病机制中的作用。
