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首页> 外文期刊>Journal of Neurophysiology >SAP102 regulates synaptic AMPAR function through a CNIH-2-dependent mechanism
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SAP102 regulates synaptic AMPAR function through a CNIH-2-dependent mechanism

机译：SAP102通过CNIH-2依赖机制调节突触AMPAR功能

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摘要

The postsynaptic density (PSD)-95-like, disk-large (DLG) membrane-associated guanylate kinase (PSD/DLG-MAGUK) family of proteins scaffold alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) complexes to the postsynaptic compartment and are postulated to orchestrate activity-dependent modulation of synaptic AMPAR functions. SAP102 is a key member of this family, present from early development, before PSD-95 and PSD-93. and throughout life. Here we investigate the role of SAP102 in synaptic transmission using a cell-restricted molecular replacement strategy, where SAP102 is expressed against the background of acute knockdown of endogenous PSD-95. We show that SAP102 rescues the decrease of AMPAR-mediated evoked excitatory postsynaptic currents (AMPAR eEPSCs) and AMPAR miniature EPSC (AMPAR mEPSC) frequency caused by acute knockdown of PSD-95. Further analysis of the mini events revealed that PSD-95-to-SAP102 replacement but not direct manipulation of PSD-95 increases the AMPAR mEPSC decay time. SAP102-mediated rescue of AMPAR eEPSCs requires AMPAR auxiliary subunit cornichon-2. whereas comichon-2 knockdown did not affect PSD-95-mediated regulation of AMPAR eEPSC. Combining these observations, our data elucidate that PSD-95 and SAP102 differentially influence basic synaptic properties and synaptic current kinetics potentially via different AMPAR auxiliary subunits.
机译：突触后密度（PSD）-95状，盘大（DLG）膜相关的胍基酶（PSD / DLG-MOMUK）蛋白质蛋白质亚氨基α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPAR）复合到突触后隔室，并假设突触AMPAR功能的协调活动依赖性调制。 SAP102是此家庭的关键成员，从早期开发，PSD-95和PSD-93之前出现。和整个生命。在这里，我们研究SAP102在使用细胞限制的分子替代策略中的突触传递中的作用，其中SAP102以内源PSD-95的急性敲低的背景表示。我们展示SAP102拯救了由PSD-95的急性敲低引起的AMPAR介导的诱发兴奋性突触电流（AMPAR EEPSCS）和AMPAR微型EPSC（AMPAR MEPSC）频率的减少。对迷你事件的进一步分析显示PSD-95-To-SAP102更换但不是直接操纵PSD-95增加了AMPAR MEPSC衰减时间。 SAP102介导的AMPAR EEPSCs的救援需要AMPAR辅助亚基Cornichon-2。虽然Comichon-2敲低度不影响PSD-95介导的AMPAR EEPSC调节。结合这些观察结果，我们的数据阐明了PSD-95和SAP102差异地通过不同的AMPAR辅助亚基差异地影响基本的突触特性和突触电流动力学。

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