Recognition coding at CNS synapses

中枢神经系统突触的识别编码

• 批准号: 7561073
• 负责人: GREG R PHILLIPS
• 金额: $ 37.03万
• 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/7561073
• 关键词: Address; Adhesions; Adhesives; Affinity; Area; Axon; Binding; Binding Proteins; Biological; Biological Assay; Biological Process; Calcium; Cell Adhesion; Cell Adhesion Molecules; Cell Communication; Cell Separation; Cell membrane; Cell physiology; Cell surface; Cells; Code; Data; Dendrites; Deposition; Embryonic Development; Exhibits; Extracellular Domain; Family; Gene Cluster; Generations; Genes; Genomics; Golgi Apparatus; Hippocampus (Brain); Intracellular Membranes; Life; Light; Maps; Mass Spectrum Analysis; Mediating; Membrane; Membrane Proteins; Modeling; Molecular; Neurites; Neurons; Organelles; Pathway interactions; Process; Property; Proteins; Role; Sorting - Cell Movement; Specificity; Synapses; Synaptic Cleft; System; Testing; Time; Work; base; extracellular; novel; postsynaptic; relating to nervous system; synaptogenesis; trafficking

Cortical synaptogenesis is thought to be initially imprecise and refined over time. We suspect that the final arrangement of CMS 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.

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。我们怀疑决赛 CMS突触的布置是根据特定的前至 突触后相互作用。通过其结合特异性，粘附分子是“分类”细胞的基础 在整个胚胎开发过程中分为组和层，并被认为在 突触发生。在突触发生过程中介导精细特异性和分选的分子是 预计将以相同类型的神经元的不可预测组合和从 相同的血统。聚集的原钙蛋白（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，可能反映出无法预测的机制 不同PCDH的组合可以在相似的神经元类型中表达。根据我们的数据和 我们的工作，我们假设PCDH是在神经元中识别“代码”的基础 控制细胞内膜结合的突触蛋白的排序以正确匹配新生 突触发生过程中的突触导致突触成熟。我们提出了两个特定目标，以测试我们的 假设。在AIM 1中，我们将确定PCDH是否实际上是粘附/识别分子和 表征其细胞质相互作用。在AIM 2中，我们将表征亚细胞贩运和 我们怀疑PCDH的PCDH的突触插入过程正确介导了正确的成熟 匹配的突触。完成这些目标后，我们希望更好地了解 突触发生中的细胞 - 细胞相互作用。