Cell Interactions in Synapes Formation and Function

突触形成和功能中的细胞相互作用

• 批准号: 6529445
• 负责人: JUAN L BRUSES
• 金额: $ 24.45万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6529445
• 关键词: cadherins; cell adhesion molecules; cell cell interaction; chickens; developmental neurobiology; electron microscopy; extracellular matrix; integrins; synapses; synaptogenesis

DESCRIPTION (provided by applicant): The long-term goal of this research program is to elucidate the cellular and molecular mechanisms that participate in the formation and function of a synaptic contact. The present proposal focuses on the role of cell adhesion in the formation of three major synaptic specializations: presynaptic terminals, active zones, and somatic spines. The primary hypothesis is that the development of adhesive linkages mediated by cell-cell and cell-matrix interactions are required for the structural organization and function of the synapse. In addition, a precise control of surface adhesion is needed for the structural modification of the synaptic junction in response to physiological stimuli. Utilizing the calyx-type synapse of the chick ciliary ganglion as an experimental model system and a retroviral system to induce molecular perturbations during development, this study will focus on the role of two families of adhesion molecules, namely the cadherins and the integrins. These molecules have been selected because of their prominent adhesive activity and expression pattern in the ciliary ganglion. The role of N-cadherin and integrins (beta1 and beta4) in the structural organization of the synapse will be investigated by perturbing their adhesive properties with wild type and mutated molecules that exert dominant negative effects. The consequences of interfering with cell adhesion will be evaluated morphologically, by analyzing the structure of the synapse at the light confocal and electron microscopic level, and functionally by assessing electrophysiologically the efficacy of synaptic transmission and the properties of the electrical currents of the ciliary neurons. The information gained from this study will lead to a better understanding of synaptogenesis and the structural requirements for synaptic function. As a variety of psychiatric and neurological disorders are believed to arise from synaptic malfunction, these studies will contribute basic knowledge toward elucidation of cellular and molecular mechanisms underlying neuropathological conditions.

描述（由申请人提供）：这项研究的长期目标 程序是阐明参与的细胞和分子机制 在突触接触的形成和功能中。目前的提议 着重于细胞粘附在三个主要突触的形成中的作用 专业：突触前末端，活动区域和躯干刺。这 主要假设是由 结构性需要细胞 - 细胞和细胞 - 矩阵相互作用 突触的组织和功能。另外，精确控制 突触的结构修饰需要表面粘附 响应生理刺激的结。 利用小鸡纤毛神经节的花萼型突触 实验模型系统和逆转录病毒系统诱导分子 开发过程中的扰动，本研究将重点关注两个 粘附分子的家族，即钙粘蛋白和整联蛋白。这些 分子之所以选择分子，是因为它们具有突出的粘合剂活性和 睫状神经节中的表达模式。 N-钙粘着蛋白和整合素（beta1和beta4）在结构中的作用 突触的组织将通过干扰其粘合剂来调查 具有野生型和突变分子的特性，具有显性阴性 效果。将评估干扰细胞粘附的后果 从形态上，通过在光线下分析突触的结构 共聚焦和电子显微镜水平，并通过评估 从电生理学上讲突触传播的功效和性能 睫状神经元的电流。 从这项研究中获得的信息将导致更好地理解 突触发生和突触功能的结构要求。作为 据信，各种精神病和神经系统疾病源于 突触故障，这些研究将为基础知识促进 阐明神经病理基础的细胞和分子机制 状况。