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: 7209706
• 负责人: JUAN L BRUSES
• 金额: $ 20.81万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 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 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7209706
• 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）：本研究的长期目标

项目成果

Adherens junctions in myelinating Schwann cells stabilize Schmidt-Lanterman incisures via recruitment of p120 catenin to E-cadherin.

有髓鞘雪旺细胞中的粘附连接通过将 p120 连环蛋白募集到 E-钙粘蛋白来稳定施密特-兰特曼切口。

• DOI: 10.1523/jneurosci.5168-04.2005
• 发表时间: 2005
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Tricaud,Nicolas;Perrin-Tricaud,Claire;Brusés,JuanL;Rutishauser,Urs
• 通讯作者: Rutishauser,Urs

Assembly of the N-cadherin complex during synapse formation involves uncoupling of p120-catenin and association with presenilin 1.

突触形成过程中 N-钙粘蛋白复合物的组装涉及 p120-连环蛋白的解偶联以及与早老素 1 的结合。

• DOI: 10.1016/j.mcn.2005.06.005
• 发表时间: 2005
• 期刊: Molecular and cellular neurosciences
• 作者: Rubio,MariaE;Curcio,Christine;Chauvet,Norbert;Bruses,JuanL
• 通讯作者: Bruses,JuanL

Polysialic acid and the formation of oculomotor synapses on chick ciliary neurons.

聚唾液酸与小鸡睫状神经元动眼神经突触的形成。

• DOI: 10.1002/cne.10199
• 发表时间: 2002
• 期刊: The Journal of comparative neurology
• 作者: Brusés,JuanL;Chauvet,Norbert;Rubio,MariaE;Rutishauser,Urs
• 通讯作者: Rutishauser,Urs

N-cadherin juxtamembrane domain modulates voltage-gated Ca2+ current via RhoA GTPase and Rho-associated kinase.

N-钙粘蛋白近膜结构域通过 RhoA GTP 酶和 Rho 相关激酶调节电压门控 Ca2 电流。

• DOI: 10.1523/jneurosci.4020-04.2004
• 发表时间: 2004
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Piccoli,Giuseppe;Rutishauser,Urs;Brusés,JuanL
• 通讯作者: Brusés,JuanL