Cytoskeleton dynamics and axon behaviour: a role for Wnt signalling

细胞骨架动力学和轴突行为：Wnt 信号传导的作用

• 批准号: BB/E016006/1
• 负责人: Patricia Salinas
• 金额: $ 54.12万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FE016006%2F1
• 关键词: Cytoskeleton; dynamics; axon; behaviour; role

The formation of a functional brain requires the assembly of appropriate nerve connections. During development, nerve cells (neurons) extend long processes called axons that grow extensively in search for their target tissue. Along their trajectory axons encounter a number of signals that elicit different responses such as attraction, pausing or repulsion. The tip of the axon or growth cone is particularly sensitive to these signals. For example, certain signals induce pausing, extension, and turning. These different responses are accomplished by the ability of these extracellular cues to 'talk' to and modify the skeleton (cytoskeleton) inside neurons. This cytoskeleton is formed by dynamic polymers that change in length, organization and direction of growth allowing nerve cells to respond quickly to changes in the environment. Although great progress has been made in the identification of large number of axon guidance cues, little is known about the mechanisms by which these extracellular cues modulate the behaviour of axons and particularly how these signals change the cytoskeleton in axons. Our laboratory has been studying the function of Wnts, molecules released by synaptic targets, in the formation of nerve connections. Wnts induce profound changes in the behaviour of axons as axons pause, form branches and change their shape when they encounter Wnt proteins. Following these changes, Wnts stimulate the formation of synapses by bringing components necessary for the release of neurotransmitters. This grant proposal addresses the mechanisms by which Wnt molecules change the behaviour of axons and the relationship with changes in the cytoskeleton. As we mainly focus on regenerating axons, our studies will new shed light into possible therapeutic strategies that can be used for nerve repair after injury.

功能性大脑的形成需要适当的神经连接的组装。在发育过程中，神经细胞（神经元）延伸称为轴突的长过程，这些轴突在寻找其靶组织时广泛生长。沿着它们的轨迹，轴突遇到许多信号，这些信号引起不同的反应，如吸引、暂停或排斥。轴突或生长锥的尖端对这些信号特别敏感。例如，某些信号引起暂停、延伸和转向。这些不同的反应是通过这些细胞外线索与神经元内的骨架（细胞骨架）“对话”和修改的能力来实现的。这种细胞骨架是由动态聚合物形成的，这些聚合物的长度、组织和生长方向会发生变化，从而使神经细胞能够对环境的变化做出快速反应。虽然已经取得了很大的进展，在确定大量的轴突导向线索，很少有人知道的机制，这些细胞外的线索调节轴突的行为，特别是这些信号如何改变轴突中的细胞骨架。我们的实验室一直在研究Wnts的功能，Wnts是由突触靶点释放的分子，在神经连接的形成中。Wnt诱导轴突行为的深刻变化，因为轴突在遇到Wnt蛋白时暂停，形成分支并改变其形状。在这些变化之后，Wnt通过带来释放神经递质所必需的成分来刺激突触的形成。这项拨款提案涉及Wnt分子改变轴突行为的机制以及与细胞骨架变化的关系。由于我们主要专注于再生轴突，我们的研究将为损伤后可用于神经修复的可能治疗策略提供新的线索。

项目成果

Activity-dependent spine morphogenesis: a role for the actin-capping protein Eps8.

• DOI: 10.1523/jneurosci.0998-12.2013
• 发表时间: 2013-02-06
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Stamatakou E;Marzo A;Gibb A;Salinas PC
• 通讯作者: Salinas PC

Wnt Signalling Promotes Actin Dynamics during Axon Remodelling through the Actin-Binding Protein Eps8.

• DOI: 10.1371/journal.pone.0134976
• 发表时间: 2015
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Stamatakou E;Hoyos-Flight M;Salinas PC
• 通讯作者: Salinas PC

Postsynaptic assembly: a role for Wnt signaling.

• DOI: 10.1002/dneu.22138
• 发表时间: 2014-08
• 期刊: DEVELOPMENTAL NEUROBIOLOGY
• 影响因子: 3
• 作者: Stamatakou, Eleanna;Salinas, Patricia C.
• 通讯作者: Salinas, Patricia C.