Mao Li-Min, Wang Qiang
Department of Basic Medical Science, School of Medicine, University of Missouri-Kansas City, Kansas City, MO 64108, USA.
J Transl Neurosci (Beijing). 2016 Sep;1(1):17-23.
Protein phosphorylation is an important posttranslational modification of group I metabotropic glutamate receptors (mGluR1 and mGluR5 subtypes) which are widely distributed throughout the mammalian brain. Several common protein kinases are involved in this type of modification, including protein kinase A, protein kinase C, and extracellular signal-regulated kinase. Through constitutive and activity-dependent phosphorylation of mGluR1/5 at specific residues, protein kinases regulate trafficking, subcellular/subsynaptic distribution, and function of modified receptors. Increasing evidence demonstrates that mGluR1/5 phosphorylation in the mesolimbic reward circuitry is sensitive to chronic psychostimulant exposure and undergoes adaptive changes in its abundance and activity. These changes contribute to long-term excitatory synaptic plasticity related to the addictive property of drugs of abuse. The rapid progress in uncovering the neurochemical basis of addiction has fostered bench-to-bed translational research by targeting mGluR1/5 for developing effective pharmacotherapies for treating addiction in humans. This review summarizes recent data from the studies analyzing mGluR1/5 phosphorylation. Phosphorylation-dependent mechanisms in stimulant-induced mGluR1/5 and behavioral plasticity are also discussed in association with increasing interest in mGluR1/5 in translational medicine.
蛋白质磷酸化是I型代谢型谷氨酸受体（mGluR1和mGluR5亚型）重要的翻译后修饰，这些受体广泛分布于整个哺乳动物脑内。几种常见的蛋白激酶参与了这类修饰，包括蛋白激酶A、蛋白激酶C和细胞外信号调节激酶。通过在特定残基处对mGluR1/5进行组成性和活性依赖性磷酸化，蛋白激酶调节修饰受体的转运、亚细胞/突触下分布及功能。越来越多的证据表明，中脑边缘奖赏回路中的mGluR1/5磷酸化对慢性精神兴奋剂暴露敏感，其丰度和活性会发生适应性变化。这些变化有助于与滥用药物成瘾特性相关的长期兴奋性突触可塑性。在揭示成瘾的神经化学基础方面的快速进展，通过将mGluR1/5作为靶点来开发治疗人类成瘾的有效药物疗法，推动了从 bench 到 bedside 的转化研究。本综述总结了分析mGluR1/5磷酸化的研究中的最新数据。还结合了转化医学中对mGluR1/5日益增长的兴趣，讨论了刺激诱导的mGluR1/5和行为可塑性中的磷酸化依赖性机制。
