ISOLATION AND CHARACTERIZATION OF SYNAPTOGENIC PROTEINS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 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。 突触形成是一个程序性发育过程，涉及由识别突触后靶点、稳定突触膜之间的接触以及突触区室之间的功能偶联所需的不同分子组进行的细胞-细胞相互作用。 由于突触是神经元通信的中心组成部分，并且在各种精神和神经系统疾病中被破坏，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系统疾病的原因。 这项建议的重点是鉴定和表征蛋白质能够诱导突触形成胚胎发育过程中。 我们的中心假设是，假定突触后神经元的膜束缚或分泌的配体的表达是诱导突触前末梢的分化和突触接触的建立所必需的。 为了这个目的，我们进行了全基因组搜索的基因，成为激活的突触发育的启动过程中在完整的动物，这导致了一组蛋白质的分子特征的蛋白质，可能参与启动突触形成的鉴定。 这个为期两年的项目将通过使用体外细胞分析来确定所鉴定的蛋白质的突触发生活性，以检查它们对神经突生长和突触前终末分化的活性。

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.