Extracellular Proteolysis in Axon Guidance and Synaptic Plasticity

建议IBN 0091184PI：克什什安，海格摘要：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，这些酶会降解或以其他方式改变局部细胞环境，从而允许改变神经元与其靶点之间的连接。其中一类重要的分泌酶是“丝氨酸蛋白酶”。这些蛋白在进化中广泛保守，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被证明是重要的。丝氨酸蛋白酶又受一种特殊的称为“丝氨酸酶”(丝氨酸酶抑制物)的蛋白质的调节。因此，蛇和丝氨酸蛋白酶是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关键作用。为了更好地了解这些蛋白质，克什希安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，克什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中表达。主要目的是检测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。果蝇神经丝蛋白与哺乳动物的神经丝蛋白关系密切，在果蝇中获得的关于其功能和调节的见解将有助于理解蛇是如何影响神经系统发育的。

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.