Genetic dissection of synaptic growth in Drosophila

果蝇突触生长的遗传解剖

• 批准号: G0802208/1
• 负责人: Iain Robinson
• 金额: $ 42.79万
• 依托单位: Plymouth University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0802208%2F1
• 关键词: Genetic; dissection; synaptic; growth; Drosophila

The body is made up of discrete individual structures known as cells which need to communicate with one another for proper function. In the brain this need for communication between cells is highly specialised and regulated. Without this high degree of specialisation complex tasks such as learning and memory, facial recognition and the perception of emotions would not exist. In the brain, individual cells are called neurones and the specialised structures that mediate communication between them, are synapses. The synaptic contacts between neuronal cells are not generally hard wired but constantly adapt to inputs from the environment. This adaptation is known as synaptic plasticity. Plastic changes in synapses occur on several levels ranging from molecular changes (the individual proteins found in cells) to morphological changes (those that alter cell shape). In order for morphological changes to persist there needs to be a rearrangement of the actin cytoskeleton which provides physical structure to cells. At a molecular level, some of the signals which act as transducers of changes in the cell?s environment are secreted from one cell and are internalised (or endocytosed) by a neighbouring cell. In this manner cell to cell signalling is achieved. Morphological changes in neurons and initial stages of endocytosis involve a deformation of lipid membranes. Thus proteins that can both deform lipids and interact with the actin cytoskeleton are likely to have key roles in regulating both synaptic architecture and function. Proteins having these attributes are the focus of this application. One goal of the application is to determine how proteins form a bridge between the lipid membranes that surround cells and the actin cytoskeleton that maintains the shape of cells and to define how these proteins regulate synaptic transmission through morphological changes. A second goal of the application is to define the molecular pathway that is needed for signal transduction to maintain synaptic contacts in the brain. In neurodegenerative diseases the strength of contact between nerve cells (the synapses) is often affected and understanding which molecules are needed to establish and maintain these contacts in normal cells is important to be able to interpret the alterations in signalling that occur in diseased cells. Loss of these connections leads to deficiencies in learning and memory, facial recognition and the ability to perceive and convey emotions; these symptoms accompany many neurodegenerative diseases. Neurodegenerative diseases are becoming more prevalent in aging populations.

身体是由离散的个体结构组成的，这些结构被称为细胞，它们需要相互沟通才能发挥正常功能。在大脑中，细胞之间的这种交流需要是高度专业化和受调节的。如果没有这种高度的专业化，学习和记忆，面部识别和情感感知等复杂任务就不会存在。在大脑中，单个细胞被称为神经元，而介导它们之间通信的专门结构是突触。神经元细胞之间的突触接触通常不是硬连线的，而是不断适应来自环境的输入。这种适应被称为突触可塑性。突触中的可塑性变化发生在几个层面上，从分子变化（细胞中发现的单个蛋白质）到形态变化（改变细胞形状的变化）。为了使形态变化持续存在，需要肌动蛋白细胞骨架的重排，从而为细胞提供物理结构。在分子水平上，一些信号作为细胞变化的传感器？的环境是从一个细胞分泌，并由相邻细胞内化（或内吞）。以这种方式，实现细胞到细胞的信号传导。神经元的形态变化和胞吞作用的初始阶段涉及脂膜的变形。因此，既能使脂质变形又能与肌动蛋白细胞骨架相互作用的蛋白质可能在调节突触结构和功能方面起关键作用。具有这些属性的蛋白质是本申请的焦点。该应用程序的一个目标是确定蛋白质如何在包围细胞的脂质膜和维持细胞形状的肌动蛋白细胞骨架之间形成桥梁，并定义这些蛋白质如何通过形态学变化调节突触传递。该应用程序的第二个目标是定义信号转导所需的分子通路，以维持大脑中的突触接触。在神经退行性疾病中，神经细胞（突触）之间的接触强度通常会受到影响，并且了解在正常细胞中建立和维持这些接触所需的分子对于能够解释患病细胞中发生的信号传导的改变是重要的。这些连接的丧失导致学习和记忆，面部识别以及感知和传达情感的能力不足;这些症状伴随着许多神经退行性疾病。神经退行性疾病在老龄化人群中越来越普遍。