DEVELOPMENTAL REGULATION OF SYNAPTIC MOLECULAR ARCHITECTURE

神经生物学中的一个中心挑战涉及到支配 神经系统中的即时通信，从属于 协调和移动等功能，以及 长期功能不足，包括学习和记忆。这个 突触，神经元之间的通讯连接，被认为是 在这些独特的神经过程中起着关键作用。 然而，值得注意的是，调节突触分子的因素 结构和大部分小说的身份或功能 突触中存在的分子仍有待确定。 越来越多的证据表明，突触后密度(PSD)是 是突触功能的中枢。尽管如此，在40种多肽中 在PSD中发现的蛋白质很少有生化特征。 然而，这些信息对于理解私营部门司的角色是必不可少的 在突触交流和可塑性方面发挥作用。通过监控少校 突触后密度蛋白(MPSDp)，我们最近证明 传入神经调节交感神经内的突触结构 大鼠颈上神经节和海马区。我们还有 外周和外周突触分子发育的明确方面 大脑。结果表明，mPSDP，一种可自我磷化的 钙/钙调蛋白依赖的蛋白激酶，是一种重要的功能， 具有可塑性的结构突触蛋白 环境刺激。 我们已经将mPSDp提纯到同质性，现在计划表征 分子水平上的新型突触蛋白。MPSDp是 在PSD中富含的一些蛋白质。同样，其他 富含PSD的蛋白质是重要角色的候选者 在突触功能上。我们建议对纯化的mPSDP进行表征 从生化和功能上详细说明。使用与以下相同的方法 MPSDp，我们寻求(1)分离、(2)表征和(3)执行 包括脑在内的另外五种蛋白质的功能研究 Dstrophin和蛋白酪氨酸激酶，在PSD中丰富。 通过对各种新的PSD蛋白的表征，我们可能会有更深入的了解 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.