DEVELOPMENTAL REGULATION OF SYNAPTIC MOLECULAR ARCHITECTURE

神经生物学的一个核心挑战是关于 神经系统中的即时通讯， 协调和运动等功能，以及 包括学习和记忆在内的长期功能。 的 突触是神经元之间的通讯连接点， 在这些独特的神经过程中发挥着关键作用。 然而，值得注意的是，调节突触分子的因子 结构和身份或功能的大部分小说 存在于突触中的分子仍有待确定。 越来越多的证据表明，突触后密度（PSD）是 突触功能的中枢 然而，在40种多肽中， 在PSD中发现，很少有蛋白质被生物化学表征。 然而，这些信息对于理解私营部门司的作用至关重要， 在突触沟通和可塑性中发挥作用。 通过监测主要 突触后密度蛋白（mPSDp），我们最近已经证明， 传入神经支配调节交感神经中的突触结构， 大鼠上级颈神经节和海马。 我们还 突触分子发育的定义方面， 个脑袋 结果表明，mPSDp，一种自磷酸化的 Ca2 +/钙调蛋白依赖性蛋白激酶，是一种功能重要的， 一种结构突触蛋白，其对 环境刺激 我们已经将mPSDp纯化至均一，现在计划表征 新的突触蛋白在分子水平上。 mPSDp是 许多蛋白质在PSD中富集。 同样，其他 在PSD中富集的蛋白质是重要作用的候选者， 在突触功能上。 我们建议将纯化的mPSDp表征为 详细的生化和功能。 使用与 mPSDp，我们寻求（1）分离，（2）表征，（3）执行 对另外五种蛋白质的功能研究，包括脑 肌营养不良蛋白和蛋白酪氨酸激酶，其在PSD中富集。 通过表征各种新的PSD蛋白，我们可以了解 突触功能和信息处理的分子基础 在神经系统中。

A central challenge in neurobiology concerns the mechanisms that govern moment-to-moment communication in the nervous system, subserving functions such as coordination and movement, and the mechanisms that underly long-term functions, including learning and memory. The synapse, the communicative junction between neurons, is acknowledged to play a pivotal role in these distinctively neural processes. Remarkably, however, the factors that regulate synaptic molecular structure and the identity or function of the majority of the novel molecules present in the synapse remain to be determined. Increasing evidence suggests that the postsynaptic density (PSD) is central to synaptic function. Nonetheless, among the 40 polypeptides found in the PSD, few proteins have been characterized biochemically. Yet this information is essential for comprehension of the roles the PSD plays in synaptic communication and plasticity. By monitoring the major postsynaptic density protein (mPSDp), we have recently demonstrated that the afferent innervation regulates synaptic structure in the sympathetic superior cervical ganglion and hippocampus of the rat. We have also defined aspects of synaptic molecular development in periphery and brain. The results suggest that the mPSDp, an autophosphorylatable Ca2+/calmodulin-dependent protein kinase, is a functionally important, structural synaptic protein exhibiting plasticity in response to environmental stimulation. We have purified the mPSDp to homogeneity and now plan to characterize the novel synaptic protein at the molecular level. The mPSDp is one of a number of proteins that is enriched in the PSD. Similarly, other proteins that are enriched in the PSD are candidates for important roles in synaptic function. We propose to characterize the purified mPSDp in detail biochemically and functionally. Using the same approaches as for mPSDp, we seek to (1) isolate, (2) characterize, and (3) perform functional studies on the five additional proteins, including brain dystrophin and protein tyrosine kinases, that are enriched in the PSD. By characterizing the various novel PSD proteins we may gain insight into the molecular basis of synaptic function and information processing in the nervous system.