Beyond the AMPA receptor: Diverse roles of SynDIG/PRRT brain-specific transmembrane proteins at excitatory synapses.
Beyond the AMPA receptor: Diverse roles of SynDIG/PRRT brain-specific transmembrane proteins at excitatory synapses.
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DOI：
10.1016/j.coph.2021.03.011
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发表时间：
2021-06
影响因子：
4
通讯作者：
Dίaz E
中科院分区：
文献类型：
--
作者：
Dίaz E
α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）型谷氨酸受体（AMPAR）负责大脑中的快速兴奋性传递。突触传递的缺陷是各种神经和精神疾病的基础。然而，鉴于AMPAR在神经传递中的核心作用，靶向AMPAR的药物开发具有挑战性。靶向AMPAR辅助因子为实现特异性而不改变基线突触传递提供了一种创新方法。本文综述了AMPAR相关跨膜蛋白的SynDIG/富含脯氨酸的跨膜蛋白（PRRT）家族。尽管这些因子基于序列相似性而相关，但这些蛋白质在兴奋性突触处已经进化出多种作用，这些作用不限于归因于AMPAR辅助因子的传统作用。SynDIG4/PRRT1作为典型的AMPAR辅助蛋白发挥作用，而PRRT2在突触前位点发挥作用以调节突触囊泡动力学，并且是人类神经系统发作性疾病的致病基因。SynDIG/PRRT蛋白是一个更大的超家族的成员，该超家族还包括已知限制宿主和病毒膜之间融合的抗病毒蛋白，并具有一些有趣的特征。
α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors (AMPARs) are responsible for fast excitatory transmission in the brain. Deficits in synaptic transmission underlie a variety of neurological and psychiatric disorders. However, drugs that target AMPARs are challenging to develop, given the central role played in neurotransmission. Targeting AMPAR auxiliary factors offers an innovative approach for achieving specificity without altering baseline synaptic transmission. This review focuses on the SynDIG/proline-rich transmembrane protein (PRRT) family of AMPAR-associated transmembrane proteins. Although these factors are related based on sequence similarity, the proteins have evolved diverse actions at excitatory synapses that are not limited to the traditional role ascribed to an AMPAR auxiliary factor. SynDIG4/PRRT1 acts as a typical AMPAR auxiliary protein, while PRRT2 functions at presynaptic sites to regulate synaptic vesicle dynamics and is the causative gene for neurological paroxysmal disorders in humans. SynDIG/PRRT proteins are members of a larger superfamily that also include antiviral proteins known to restrict fusion between host and viral membranes and share some interesting characteristics.
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