Extracellular Proteolysis in Axon Guidance and Synaptic Plasticity

轴突引导和突触可塑性中的细胞外蛋白水解

• 批准号: 0091184
• 负责人: Haig Keshishian
• 金额: $ 37.2万
• 依托单位: Yale University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-03-01 至 2004-02-29
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0091184&HistoricalAwards=false
• 关键词: Extracellular; Proteolysis; Axon; Guidance; Synaptic

Proposal IBN 0091184PI: Keshishian, HaigAbstract:One of the ways a nervous system undergoes change is to modify the connections between nerve cells. This often requires the action of specialized secreted enzymes, which degrade or otherwise modify the local cellular environment, thus permitting modifications in the connections between neurons and their targets. An important class of these secreted enzymes is the "serine proteinases". These proteinases are widely conserved in evolution, and have been shown to be important in both the establishment and modification of neural connections during development, as well as in the later modifications associated with learning and memory. Serine proteinases are in turn regulated by a special class of proteins known as "serpins" (serine proteinase inhibitors). The serpins and serine proteinases, therefore, function as an interdependent system of secreted proteins of key importance in regulating nervous system change. In order to understand these proteins better Dr. Keshishian will examine their biological functions in a model genetic system, Drosophila. In Drosophila Dr. Keshishian has already identified the key "neuroserpin" of the nervous system, and has noted that it is expressed at connections between motoneurons and muscles. The major goal is to examine its functions at the developing neuromuscular connections, and to test the effects of both its loss and overexpression. The Drosophila neuroserpin is closely related to its mammalian counterpart, and insights gained in Drosophila about its function and regulation will be of value in understanding how the serpins influence nervous system development in general.

摘要：神经系统发生变化的方式之一是改变神经细胞之间的连接。这通常需要特殊的分泌酶的作用，这些酶降解或以其他方式改变局部细胞环境，从而允许神经元与其目标之间的连接发生改变。这些分泌酶的一个重要类别是“丝氨酸蛋白酶”。这些蛋白酶在进化过程中广泛保守，并已被证明在发育过程中神经连接的建立和修改以及后来与学习和记忆相关的修改中都很重要。丝氨酸蛋白酶依次受到一类特殊蛋白质的调节，这种蛋白质被称为“丝氨酸蛋白酶抑制剂”。因此，丝氨酸蛋白酶和丝氨酸蛋白酶作为一个相互依赖的分泌蛋白系统，在调节神经系统变化中起着至关重要的作用。为了更好地了解这些蛋白质，Keshishian博士将在果蝇模型遗传系统中研究它们的生物学功能。在果蝇中，凯希安博士已经确定了神经系统的关键“神经丝氨酸蛋白”，并注意到它在运动神经元和肌肉之间的连接处表达。主要目标是检查其在发育中的神经肌肉连接中的功能，并测试其缺失和过度表达的影响。果蝇的神经蛇形蛋白与哺乳动物的神经蛇形蛋白密切相关，在果蝇中获得的关于其功能和调节的见解将对理解蛇形蛋白如何影响神经系统的发育具有价值。