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

这项研究旨在了解神经系统模式形成的机制。它集中在这个系统内神经元复杂排列和相互连接的形成中所涉及的细胞机制。在发育过程中，神经元延伸神经元突起，寻找需要与之建立联系的细胞。在与他们的目标接触后，突触被组装起来，允许神经元之间的交流。突触不是稳定的结构，而是动态的，不断地经历形状变化。这些形状的变化由细胞骨架的变化控制，细胞骨架主要由肌动蛋白细丝组成。事实上，对肌动蛋白细丝的直接干扰阻止了突触的形状变化，并损害了神经元的交流。通过细胞内脂质信号的变化，已知磷酸酶PTEN可以改变突触的形态。事实上，许多神经疾病都与这一信号通路的放松有关。然而，尚不清楚这一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。这项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。

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.