ISOLATION AND CHARACTERIZATION OF SYNAPTOGENIC PROTEINS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这些研究的长期目标是阐明调节突触接触形成的分子机制。突触的形成是一种程序化的发育过程，细胞间的相互作用由识别突触后靶点、稳定突触膜之间的接触和突触间隔之间的功能耦合所需的不同分子群执行。由于突触是神经元交流的中心组成部分，在各种精神和神经疾病中都会受到干扰，因此识别参与建立突触连接的分子机制将有助于我们理解神经元回路的形成以及精神和神经疾病的原因。 这项建议的重点是鉴定和鉴定能够在胚胎发育过程中诱导突触形成的蛋白质。我们的中心假设是，假定突触后神经元表达膜系留或分泌配体是诱导突触前终末分化和建立突触联系所必需的。为此，我们在全基因组范围内搜索在完整动物的突触发育启动过程中被激活的基因，从而鉴定出一组具有可能参与突触形成的蛋白质的分子特征的蛋白质。这个为期两年的项目将通过使用体外细胞分析来检测它们在突触生长和突触前终末分化方面的活性，以确定识别出的蛋白质的突触生成活性。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The long-term goal of these studies is to elucidate the molecular mechanisms that regulate the formation of synaptic contacts. Synapse formation is a well-programmed developmental process involving cell-cell interactions carried out by distinct groups of molecules required for recognition of postsynaptic targets, stabilization of the contact between synaptic membranes, and functional coupling between synaptic compartments. As synapses are the central component of neuronal communication and are disrupted in a variety of mental and neurological disorders, the identification of the molecular mechanisms that participate in the establishment of synaptic connections will contribute to our understanding of the formation of neuronal circuits and the causes of mental and neurological diseases. This proposal focuses on the identification and characterization of proteins capable of inducing synapse formation during embryogenesis. Our central hypothesis is that the expression of membrane tethered or secreted ligands by presumptive postsynaptic neurons is required to induce the differentiation of the presynaptic terminal and the establishment of a synaptic contact. To this aim, we carried out a genome-wide search of genes that become activated during the initiation of synapse development in the intact animal, which led to the identification of a group of proteins having the molecular features of proteins that may participate in the initiation of synapse formation. This two-year project will determine the synaptogenic activity of the identified proteins by using in vitro cell assays to examine their activity on neurite outgrowth and presynaptic terminal differentiation.