Recognition coding at CNS synapses

皮质突触发生被认为最初是不精确的，并随着时间的推移而完善。我们怀疑， CMS突触的排列是基于特定的预处理的“排序”或“重排”的示例。 突触后相互作用通过它们的结合特异性，粘附分子是“分选”细胞的基础 在整个胚胎发育过程中分成群体和层，并被认为在胚胎发育过程中起着类似的作用。 突触发生也是如此。在突触发生过程中介导精细特异性和分选的分子是 预期在相同类型的神经元中以不可预测的组合差异表达， 同样的血统。成簇原钙粘蛋白（Pcdhs），新的假定神经粘附/识别 分子，表现出预期的介导精确水平的突触识别的分子的性质。 他们的基因被组织成不寻常的簇，这可能反映了不可预测的 不同Pcdhs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 在其他人的工作中，我们假设Pcdhs是神经元之间识别“代码”的基础， 控制细胞内膜结合突触蛋白的分选以正确匹配新生突触蛋白， 在突触发生过程中的突触，导致突触成熟。我们提出了两个具体目标，以测试我们的 假说.在目标1中，我们将确定Pcdhs是否实际上是粘附/识别分子， 表征它们的细胞质相互作用。在目标2中，我们将描述亚细胞运输的特征， Pcdh的突触插入过程，我们怀疑是Pcdh正确介导的成熟的基础。 匹配的突触在完成这些目标后，我们希望能更好地了解 突触发生中的细胞间相互作用。

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.