SynDIG4/Prrt1 Is Required for Excitatory Synapse Development and Plasticity Underlying Cognitive Function.
SynDIG4/Prrt1 Is Required for Excitatory Synapse Development and Plasticity Underlying Cognitive Function.
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DOI：
10.1016/j.celrep.2018.02.026
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发表时间：
2018-02-27
期刊：
影响因子：
8.8
通讯作者：
Díaz E
中科院分区：
文献类型：
--
作者：
Matt L;Kirk LM;Chenaux G;Speca DJ;Puhger KR;Pride MC;Qneibi M;Haham T;Plambeck KE;Stern-Bach Y;Silverman JL;Crawley JN;Hell JW;Díaz E
突触中改变AMPA受体（AMPAR）含量是在学习和记忆过程中突触强度调节的关键机制。先前的工作表明Syndig1（突触分化诱导的基因1）编码了跨膜AMPAR相关的蛋白质，该蛋白调节兴奋性突触强度和数量。在这里，我们表明，相关的蛋白质Syndig4（也称为PRRT1）以亚基依赖性方式修饰AMPAR门控性能。通过免疫细胞化学和电生理学评估，年轻的Syndig4敲除（KO）小鼠的兴奋性突触较弱。成年Syndig4 KO小鼠显示破伤风诱导的长期增强（LTP）完全丧失，而MEPSC幅度仅降低了25％。此外，Syndig4 KO小鼠在两个独立的认知测定中表现出缺陷。鉴于Syndig4与非突触部位的AMPAR亚基GLUA1共定位，我们建议Syndig4维持突触发育和基础高阶认知可塑性基础功能所必需的外突触外AMPAR池。
Matt等。表明缺乏与AMPAR相关的蛋白Syndig4/prrt1的小鼠在突触可塑性和认知中显示缺陷。 Syndig4修饰了异源细胞中AMPAR生物物理特性，但突触AMPAR动力学却没有变化，这表明Syndig4建立了高阶认知可塑性所需的一系列外部抗肌外AMPAR。
Altering AMPA receptor (AMPAR) content at synapses is a key mechanism underlying the regulation of synaptic strength during learning and memory. Previous work demonstrated that SynDIG1 (synapse differentiation-induced gene 1) encodes a transmembrane AMPAR-associated protein that regulates excitatory synapse strength and number. Here we show that the related protein SynDIG4 (also known as Prrt1) modifies AMPAR gating properties in a subunit-dependent manner. Young SynDIG4 knockout (KO) mice have weaker excitatory synapses, as evaluated by immunocytochemistry and electrophysiology. Adult SynDIG4 KO mice show complete loss of tetanus-induced long-term potentiation (LTP), while mEPSC amplitude is reduced by only 25%. Furthermore, SynDIG4 KO mice exhibit deficits in two independent cognitive assays. Given that SynDIG4 colocalizes with the AMPAR subunit GluA1 at non-synaptic sites, we propose that SynDIG4 maintains a pool of extrasynaptic AMPARs necessary for synapse development and function underlying higher-order cognitive plasticity. Matt et al. show that mice lacking the AMPAR-associated protein SynDIG4/Prrt1 display deficits in synaptic plasticity and cognition. SynDIG4 modifies AMPAR biophysical properties in heterologous cells, but synaptic AMPAR kinetics are unchanged, suggesting that SynDIG4 establishes a pool of extrasynaptic AMPARs necessary for higher-order cognitive plasticity.
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