Control of the actin cytoskeleton by PI3K/PTEN signalling during dendritic remodelling

树突重塑过程中 PI3K/PTEN 信号传导对肌动蛋白细胞骨架的控制

• 批准号: BB/F015321/1
• 负责人: Britta Eickholt
• 金额: $ 43.8万
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2008
• 资助国家: 英国
• 起止时间: 2008 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FF015321%2F1
• 关键词: Control; actin; cytoskeleton; PI3K; PTEN

This research is directed at understanding the mechanisms of the patterning of the nervous system. It focuses on the cellular mechanisms that are involved in the formation of the complex arrangement and interconnection of the neurons within this system. During the process of development, neurons extend neuronal processes, which seek out the cells that they need to establish connection with. Following contact with their target, synapses are assembled which allow the communication between neurons. Rather than being stable structures, synapses are dynamic and continuously undergo shape changes. These changes in shape are controlled by changes in the cytoskeleton, which mainly consists of actin filaments. Indeed, direct interference with the actin filaments blocks shape changes of the synapse and impairs neuronal communication. Through changes in intracellular lipid signalling, the phosphatase PTEN is known to alter the morphology of synapses. In fact, many neurological conditions are associated with a deregulation of this signalling pathway. What is not known, however, is how this signalling pathway controls changes of the actin cytoskeleton, leading to altered synapse shapes. This research will investigate the mechanisms that control the actin cytoskeleton during changes in lipid signalling.

这项研究旨在了解神经系统模式的机制。它侧重于参与该系统内神经元的复杂排列和互连的形成的细胞机制。在发育过程中，神经元延伸神经元过程，寻找它们需要建立连接的细胞。在与它们的目标接触之后，突触被组装，从而允许神经元之间的通信。突触不是稳定的结构，而是动态的，不断经历形状变化。这些形状的变化是由细胞骨架的变化控制的，细胞骨架主要由肌动蛋白丝组成。事实上，直接干扰肌动蛋白丝会阻碍突触的形状变化，并损害神经元的通讯。通过细胞内脂质信号的变化，磷酸酶PTEN已知改变突触的形态。事实上，许多神经系统疾病都与这种信号通路的失调有关。然而，目前尚不清楚的是，这种信号通路如何控制肌动蛋白细胞骨架的变化，从而导致突触形状的改变。本研究将探讨在脂质信号变化过程中控制肌动蛋白细胞骨架的机制。

项目成果

Phosphorylation of the actin binding protein Drebrin at S647 is regulated by neuronal activity and PTEN.

• DOI: 10.1371/journal.pone.0071957
• 发表时间: 2013
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Kreis P;Hendricusdottir R;Kay L;Papageorgiou IE;van Diepen M;Mack T;Ryves J;Harwood A;Leslie NR;Kann O;Parsons M;Eickholt BJ
• 通讯作者: Eickholt BJ