Swope S L, Moss S J, Blackstone C D, Huganir R L
Department of Neuroscience, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
FASEB J. 1992 May;6(8):2514-23.
Most neurotransmitter receptors examined to date have been shown either to be regulated by protein phosphorylation or to contain consensus sequences for phosphorylation by protein kinases. Neurotransmitter receptors that mediate rapid synaptic transmission in the nervous system are the ligand-gated ion channels and include the nicotinic acetylcholine receptors of muscle and nerve and the excitatory and inhibitory amino acid receptors: the glutamate, GABAA, and glycine receptors. These receptors are multimeric proteins composed of homologous subunits which each span the membrane several times and contain a large intracellular loop that is a mosaic of consensus sites for protein phosphorylation. Recent evidence has suggested that extracellular signals released from the presynaptic neuron, such as neurotransmitters and neuropeptides as well as an extracellular matrix protein, regulate the phosphorylation of ligand-gated ion channels. The functional effects of phosphorylation are varied and include the regulation of receptor desensitization rate, subunit assembly, and receptor aggregation at the synapse. These results suggest that phosphorylation of neurotransmitter receptors represents a major mechanism in the regulation of their function and may play an important role in synaptic plasticity.
迄今为止，已检测的大多数神经递质受体均显示出要么受蛋白质磷酸化调节，要么含有蛋白激酶磷酸化的共有序列。介导神经系统快速突触传递的神经递质受体是配体门控离子通道，包括肌肉和神经中的烟碱型乙酰胆碱受体以及兴奋性和抑制性氨基酸受体：谷氨酸受体、GABAA受体和甘氨酸受体。这些受体是由同源亚基组成的多聚体蛋白，每个亚基跨膜数次，并含有一个大的细胞内环，该环是蛋白质磷酸化共有位点的镶嵌体。最近的证据表明，突触前神经元释放的细胞外信号，如神经递质、神经肽以及一种细胞外基质蛋白，可调节配体门控离子通道的磷酸化。磷酸化的功能效应多种多样，包括调节受体脱敏速率、亚基组装以及突触处的受体聚集。这些结果表明，神经递质受体的磷酸化是调节其功能的主要机制，可能在突触可塑性中发挥重要作用。
