Recognition coding at CNS synapses

中枢神经系统突触的识别编码

• 批准号: 7143574
• 负责人: GREG R PHILLIPS
• 金额: $ 19.07万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-02 至 2011-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7143574
• 关键词: adhesions; intracellular; neurons; proteins; synapses; synaptogenesis

DESCRIPTION (provided by applicant): Cortical synaptogenesis is thought to be initially imprecise and refined over time. We suspect that the final arrangement of CNS synapses is an example of "sorting" or "reshuffling" based on specific pre-to- postsynaptic interactions. Via their binding specificity, adhesion molecules are the basis for "sorting" cells into groups and layers throughout embryonic development and have been thought to function similarly during synaptogenesis as well. Molecules that mediate fine specificity and sorting during synaptogenesis are expected to be differentially expressed in unpredictable combinations in neurons of the same type and from the same lineages. The clustered protocadherins (Pcdhs), novel putative neural adhesion/recognition molecules, exhibit properties expected of molecules that mediate a precise level of synaptic recognition. Their genes are organized into unusual clusters that may reflect the mechanism by which unpredictable combinations of different Pcdhs can be expressed within similar neuronal types. Based on our data and work from others, we hypothesize that the Pcdhs are a basis for a recognition "code" among neurons by controlling the sorting of intracellular membrane bound synaptic proteins to correctly matched nascent synapses during synaptogenesis resulting in synaptic maturation. We propose two Specific Aims to test our hypothesis. In Aim 1, we will determine whether Pcdhs are actually adhesion/recognition molecules and characterize their cytoplasmic interactions. In Aim 2, we will characterize the subcellular trafficking and synaptic insertion processes of the Pcdhs that we suspect underlie Pcdh mediated maturation of correctly matched synapses. Upon completion of these Aims we expect to have a better understanding of the role of cell-cell interactions in synaptogenesis.

描述（由申请人提供）：皮质突触发生被认为最初是不精确的，并且随着时间的流逝而精致。我们怀疑中枢神经系统突触的最终布置是基于特定前后突触后相互作用的“排序”或“改组”的示例。通过它们的结合特异性，粘附分子是整个胚胎发育中“分类”细胞分为组和层的基础，并且在突触发生过程中也被认为具有相似的功能。预计在相同类型和同一谱系中的神经元中，在不可预测的组合中，预期介导精细特异性和分选的分子被差异表达。簇状的原钙蛋白（PCDHS），新型假定的神经粘附/识别分子，表现出介导精确水平的突触识别水平的分子所期望的特性。它们的基因被组织成异常的簇，这些簇可能反映出可以在相似的神经元类型中表达不同PCDH的不可预测组合的机制。基于我们的数据和其他工作，我们假设PCDH是通过控制细胞内膜结合的突触蛋白的排序在神经元中识别神经元中识别“代码”的基础，以在突触成熟过程中正确匹配突触中的新生突触。我们提出了两个特定的目的来检验我们的假设。在AIM 1中，我们将确定PCDH是否实际上是粘附/识别分子并表征其细胞质相互作用。在AIM 2中，我们将表征我们怀疑PCDH基础的PCDH的亚细胞运输和突触插入过程，介导了正确匹配的突触的成熟。完成这些目标后，我们期望更好地了解细胞 - 细胞相互作用在突触发生中的作用。