Exploring the F-actin/CPEB3 interaction and its possible role in the molecular mechanism of long-term memory
Exploring the F-actin/CPEB3 interaction and its possible role in the molecular mechanism of long-term memory
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DOI：
10.1073/pnas.2012964117
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发表时间：
2020-09-08
影响因子：
11.1
通讯作者：
Wolynes, Peter G.
中科院分区：
文献类型：
--
作者：
Gu, Xinyu;Schafer, Nicholas P.;Wolynes, Peter G.
树突棘是神经元树突上微小的膜性突起。树突棘会根据输入信号改变形状，从而加强神经元之间的联系。树突棘的生长和稳定被认为是维持长期记忆的关键。脊椎中肌动蛋白细胞骨架的重塑是其形成和生长的关键因素。更推测的是，CPEB3的聚集被报道参与了长期记忆的维持。CPEB3是一种结合RNA的功能性普恩病毒。在这里，我们研究了肌动蛋白和CPEB3之间的相互作用，并提出了CPEB3和肌动蛋白细丝(F-肌动蛋白)的复杂结构的分子模型。我们的计算模型的结果，包括能量和结构分析，与来自肽阵列实验的新数据进行了比较。我们的CPEB3/F-肌动蛋白相互作用模型表明，F-肌动蛋白通过将CPEB3短序列压缩成β-发夹形式，潜在地触发了短序列易于聚集的结构转变。我们还提出，CPEB3/F-肌动蛋白的相互作用可能受到CPEB3的SUMO化的调节，这是基于对CPEB3中潜在的SUMO位点以及SUMO相互作用基序的生物信息学搜索。在这些结果和现有文献的基础上，我们提出了一个可能的长时记忆的分子机制，即CPEB3的S与肌动蛋白结合，它的聚集，以及它的SUMO化调节。
Dendritic spines are tiny membranous protrusions on the dendrites of neurons. Dendritic spines change shape in response to input signals, thereby strengthening the connections between neurons. The growth and stabilization of dendritic spines is thought to be essential for maintaining long-term memory. Actin cytoskeleton remodeling in spines is a key element of their formation and growth. More speculatively, the aggregation of CPEB3, a functional prion that binds RNA, has been reported to be involved in the maintenance of long-term memory. Here we study the interaction between actin and CPEB3 and propose a molecular model for the complex structure of CPEB3 and an actin filament (F-actin). The results of our computational modeling, including both energetic and structural analyses, are compared with novel data from peptide array experiments. Our model of the CPEB3/F-actin interaction suggests that F-actin potentially triggers the aggregation-prone structural transition of a short CPEB3 sequence by zipping it into a beta-hairpin form. We also propose that the CPEB3/F-actin interaction might be regulated by the SUMOylation of CPEB3, based on bioinformatic searches for potential SUMOyIation sites as well as SUMO interacting motifs in CPEB3. On the basis of these results and the existing literature, we put forward a possible molecular mechanism underlying long-term memory that involves CPEB3's binding to actin, its aggregation, and its regulation by SUMOylation.