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: 6641221
• 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/6641221
• 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(申请人提供)：本研究的长期目标 程序是为了阐明参与其中的细胞和分子机制 在突触接触的形成和功能中。目前的建议 重点阐述了细胞黏附在三种主要突触形成中的作用 特化：突触前终末、活动区和体细胞脊椎。这个 主要的假设是粘性连接的发展是由 细胞-细胞和细胞-基质相互作用是结构所必需的 突触的组织和功能。此外，精准控制 突触的结构修饰需要表面黏附 对生理刺激作出反应的连接。 利用雏鸡睫状神经节的花帽型突触作为 诱导分子的实验模型系统和逆转录病毒系统 在发展过程中的扰动，本研究将重点研究两个方面的作用 黏附分子家族，即钙粘附素和整合素。这些 分子之所以被选中，是因为它们具有显著的粘合活性和 睫状神经节的表达模式。 N-钙粘附素和整合素(β_1和β_4)在结构调控中的作用 通过干扰突触的粘附物来研究突触的组织 表现出显性负值的野生型和突变分子的性质 效果。将对干扰细胞黏附的后果进行评估 在形态上，通过分析光下突触的结构 共聚焦和电子显微镜水平，并通过评估功能 突触传递的电生理学效应及其特性 睫状神经细胞的电流。 从这项研究中获得的信息将有助于更好地理解 突触发生和突触功能的结构要求。作为一名 各种精神和神经障碍被认为是由 突触功能障碍，这些研究将有助于为 神经病理基础的细胞和分子机制的阐明 条件。