Division of Neuroscience, Biomedical Sciences Research Centre "Alexander Fleming," Vari 16672, Greece.
Division of Neuroscience, Biomedical Sciences Research Centre "Alexander Fleming," Vari 16672, Greece
Proc Natl Acad Sci U S A. 2017 Oct 10;114(41):10984-10989. doi: 10.1073/pnas.1704835114. Epub 2017 Sep 25.
Anesthesia-resistant memory (ARM) was described decades ago, but the mechanisms that underlie this protein synthesis-independent form of consolidated memory in remain poorly understood. Whether the several signaling molecules, receptors, and synaptic proteins currently implicated in ARM operate in one or more pathways and how they function in the process remain unclear. We present evidence that Drk, the ortholog of the adaptor protein Grb2, is essential for ARM within adult mushroom body neurons. Significantly, Drk signals engage the Rho kinase Drok, implicating dynamic cytoskeletal changes in ARM, and this is supported by reduced F-actin in the mutants and after pharmacological inhibition of Drok. Interestingly, Drk-Drok signaling appears independent of the function of Radish (Rsh), a protein long implicated in ARM, suggesting that the process involves at least two distinct molecular pathways. Based on these results, we propose that signaling pathways involved in structural plasticity likely underlie this form of translation-independent memory.
抗麻醉性记忆 (ARM) 几十年前就被描述过，但在 中，这种与蛋白质合成无关的巩固记忆形式的基础机制仍未得到很好的理解。目前涉及 ARM 的几种信号分子、受体和突触蛋白是否在一个或多个途径中起作用，以及它们在该过程中如何发挥作用尚不清楚。我们提供的证据表明，衔接蛋白 Grb2 的直系同源物 Drk 对于成年蘑菇体神经元中的 ARM 是必不可少的。重要的是，Drk 信号激活 Rho 激酶 Drok，这表明在 ARM 中涉及动态细胞骨架变化，这一结果得到了突变体中 F-肌动蛋白减少和 Drok 药理学抑制后的支持。有趣的是，Drk-Drok 信号似乎独立于 Radish（Rsh）的功能，Rsh 长期以来一直被认为与 ARM 有关，这表明该过程涉及至少两种不同的分子途径。基于这些结果，我们提出参与结构可塑性的信号通路可能是这种不依赖于翻译的记忆形式的基础。
