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Ras and Rap Signal Bidirectional Synaptic Plasticity via Distinct Subcellular Microdomains

机译:通过不同的亚细胞微粒瘤,RA和RAP信号双向突触塑性度

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摘要

How signaling molecules achieve signal diversity and specificity is a long-standing cell biology question. Here we report the development of a targeted delivery method that permits specific expression of?homologous Ras-family small GTPases (i.e., Ras, Rap2, and Rap1) in different subcellular microdomains, including the endoplasmic reticulum, lipid rafts, bulk membrane, lysosomes, and Golgi complex, in rodent hippocampal CA1 neurons. The microdomain-targeted delivery, combined with multicolor fluorescence protein tagging and high-resolution dual-quintuple simultaneous patch-clamp recordings, allows systematic analysis of microdomain-specific signaling. The analysis shows?that Ras signals long-term potentiation via endoplasmic reticulum PI3K and lipid raft ERK, whereas Rap2 and Rap1 signal depotentiation and long-term depression via bulk membrane JNK and lysosome p38MAPK, respectively. These results establish an effective subcellular microdomain-specific targeted delivery method?and unveil subcellular microdomain-specific signaling as the mechanism for homologous Ras and Rap to achieve signal diversity and specificity to control multiple forms of synaptic plasticity.
机译:信号分子如何实现信号多样性和特异性是一个长期的细胞生物学问题。在这里,我们举报了允许特异性表达的目标递送方法?在不同亚细胞微膜中的同源RAS家族小GTP酶(即RAS,RAP2和RAP1),包括内质网,脂质筏,散装膜,溶酶体,啮齿动物海马Ca1神经元和戈尔加复合物。微米映射靶向递送,结合多色荧光蛋白标记和高分辨率双通道同时贴片夹具,允许系统分析特定的微米信号。分析显示?RA通过内质网PI3K和脂质筏ERK的长期增强,而RAP2和RAP1通过散装膜JNK和溶酶体P38MAPK的长期抑郁。这些结果建立了有效的亚细胞微米特异性靶向递送方法?并且揭示亚细胞微莫莫族特异性信令作为同源RAS的机制,并且RAP实现信号分集和特异性来控制多种形式的突触塑性。

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