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PRRT1 regulates basal and plasticity-induced AMPA receptor trafficking.
Molecular and Cellular Neuroscience ( IF 3.5 ) Pub Date : 2019-06-16 , DOI: 10.1016/j.mcn.2019.06.008
Eva Troyano-Rodriguez 1 , Shivani Mann 1 , Raja Ullah 1 , Mohiuddin Ahmad 1
Affiliation  

AMPA-type glutamate receptors (AMPAR) are one of the principal mediators of fast excitatory synaptic transmission in the brain. These receptors associate with multiple integral membrane proteins which influence their trafficking and channel properties. Proline-rich transmembrane protein 1 (PRRT1) is a membrane protein and an understudied component of native AMPAR complexes. In order to understand the regulation of AMPARs by PRRT1, we have performed electrophysiological and biochemical investigations on acute hippocampal slices derived from PRRT1 knockout mice. Our results show that PRRT1 controls the levels of AMPARs at the cell surface, though it is dispensable for synaptic transmission. PRRT1 has differential effects on the stability of AMPAR GluA1 subunit phosphorylated at S845 and at S831, two residues at which the phosphorylation status has major influences on receptor trafficking. Furthermore, PRRT1 is required for NMDA receptor-dependent long-term depression (LTD) and proper NMDA-induced AMPAR trafficking. These findings position PRRT1 as an important regulator of AMPAR stabilization and trafficking in different subcellular pools under basal conditions and during synaptic plasticity.

中文翻译:

PRRT1调节基础和可塑性诱导的AMPA受体运输。

AMPA型谷氨酸受体(AMPAR)是大脑中快速兴奋性突触传递的主要介质之一。这些受体与多个完整的膜蛋白缔合,这些蛋白会影响它们的运输和通道特性。富含脯氨酸的跨膜蛋白1(PRRT1)是一种膜蛋白,是天然AMPAR复合物的未充分研究的组成部分。为了了解PRRT1对AMPAR的调节,我们对源自PRRT1基因敲除小鼠的急性海马切片进行了电生理和生化研究。我们的结果表明,PRRT1控制细胞表面AMPAR的水平,尽管它对于突触传递是必不可少的。PRRT1对在S845和S831磷酸化的AMPAR GluA1亚基的稳定性有不同的影响,两个残基的磷酸化状态对受体的运输有重要影响。此外,PRRT1是NMDA受体依赖性长期抑郁症(LTD)和适当的NMDA诱导的AMPAR转运所必需的。这些发现将PRRT1定位为基础条件下和突触可塑性期间AMPAR稳定和在不同亚细胞池中运输的重要调节剂。
更新日期:2019-06-16
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