Retinoic Acid and LTP Recruit Postsynaptic AMPA Receptors Using Distinct SNARE-Dependent Mechanisms.
Retinoic Acid and LTP Recruit Postsynaptic AMPA Receptors Using Distinct SNARE-Dependent Mechanisms.
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DOI：
10.1016/j.neuron.2015.03.009
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发表时间：
2015-04-22
期刊：
影响因子：
16.2
通讯作者：
Chen L
中科院分区：
文献类型：
--
作者：
Arendt KL;Zhang Y;Jurado S;Malenka RC;Südhof TC;Chen L
视黄酸（RA）依赖的稳态可塑性和NMDA受体依赖的LTP（一种Hebbian可塑性）都通过增加突触后AMPA受体（AMPAR）的丰度来增强突触强度。然而，目前还不清楚在稳态和Hebbian可塑性过程中介导AMPAR运输的分子机制是否不同，也不知道RA信号如何影响Hebbian可塑性。在这里，我们表明，RA增加突触后AMPAR丰度的活动依赖的机制，需要一个独特的陷阱依赖的融合机制不同，介导的LTP。具体而言，RA诱导的AMPAR运输不涉及复合蛋白，其激活含有突触融合蛋白-1或-3的SNARE复合物，但不激活含有突触融合蛋白-4的复合物，而LTP需要复合蛋白。此外，RA诱导的AMPAR运输利用了Q-SNARE syntaxin-4，而LTP利用了syntaxin-3;两者还需要Q-SNARE SNAP-47和R-SNARE synatobrevin-2。最后，急性RA治疗阻断了随后的LTP表达，可能是通过增加AMPAR贩运。因此，RA诱导的稳态可塑性涉及一种新的，活性依赖性突触后AMPAR运输途径介导的独特的SNARE依赖性融合机制。
Retinoic acid- (RA-) dependent homeostatic plasticity and NMDA-receptor-dependent LTP, a form of Hebbian plasticity, both enhance synaptic strength by increasing the abundance of postsynaptic AMPA receptors (AMPARs). However, it is unclear whether the molecular mechanisms mediating AMPAR-trafficking during homeostatic and Hebbian plasticity differ, and unknown how RA-signaling impacts Hebbian plasticity. Here, we show that RA increases postsynaptic AMPAR-abundance by an activity-dependent mechanism that requires a unique SNARE-dependent fusion machinery different from that mediating LTP. Specifically, RA-induced AMPAR-trafficking did not involve complexin, which activates SNARE complexes containing syntaxin-1 or -3 but not complexes containing syntaxin-4, whereas LTP required complexin. Moreover, RA-induced AMPAR trafficking utilized the Q-SNARE syntaxin-4 whereas LTP utilized syntaxin-3; both additionally required the Q-SNARE SNAP-47 and the R-SNARE synatobrevin-2. Finally, acute RA treatment blocked subsequent LTP expression, probably by increasing AMPAR-trafficking. Thus, RA-induced homeostatic plasticity involves a novel, activity-dependent postsynaptic AMPAR-trafficking pathway mediated by a unique SNARE-dependent fusion machinery.