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Drk-mediated signaling to Rho kinase is required for anesthesia-resistant memory in Drosophila
Proceedings of the National Academy of Sciences of the United States of America ( IF 9.4 ) Pub Date : 2017-09-25 00:00:00 , DOI: 10.1073/pnas.1704835114
Vasileia Kotoula 1 , Anastasios Moressis 1 , Ourania Semelidou 1 , Efthimios M. C. Skoulakis 1
Affiliation  

Anesthesia-resistant memory (ARM) was described decades ago, but the mechanisms that underlie this protein synthesis-independent form of consolidated memory in Drosophila 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 Drosophila 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.

中文翻译:

果蝇中抗麻醉性记忆需要Drk介导的Rho激酶信号转导

麻醉耐受性记忆(ARM)在几十年前就已被描述,但是果蝇这种蛋白质合成非依赖型整合记忆形式的基础机制仍然知之甚少。目前涉及ARM的几种信号分子,受体和突触蛋白是否以一种或多种途径起作用,以及它们在该过程中如何发挥作用尚不清楚。我们提供证据证明果蝇Drk衔接蛋白Grb2的直系同源物,对于成年蘑菇体神经元内的ARM是必不可少的。重要的是,Drk信号与Rho激酶Drok结合,暗示ARM中的动态细胞骨架变化,并且突变体中F-肌动蛋白减少以及药理抑制了Drok后,这种情况得到了支持。有趣的是,Drk–Drok信号的出现似乎与Radish(Rsh)的功能无关,该蛋白长期与ARM有关,表明该过程涉及至少两个不同的分子途径。基于这些结果,我们建议涉及结构可塑性的信号转导通路可能是这种形式的独立于翻译的记忆的基础。
更新日期:2017-09-26
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