Recognition coding at CNS synapses

大脑皮层突触发生最初被认为是不精确的，并随着时间的推移而细化。我们怀疑决赛 CMS突触的排列是基于特定的Pre-to-Th的“排序”或“重新洗牌”的例子 突触后的相互作用。由于其结合的特异性，黏附分子是细胞“分选”的基础 在整个胚胎发育过程中形成组和层，并被认为在 突触发生也是如此。在突触发生过程中调节细微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方式差异表达 同样的血统。聚集型原钙粘附素(Pcdhs)--新的神经黏附/识别机制 分子，表现出分子应有的特性，调节精确的突触识别水平。 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 根据其他人的研究，我们假设Pcdhs是神经元之间识别“代码”的基础，通过 控制细胞内膜结合突触蛋白的分选以正确匹配新生细胞 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来测试我们的 假设。在目标1中，我们将确定Pcdhs是否实际上是黏附/识别分子和 描述它们的细胞质相互作用。在目标2中，我们将描述亚细胞贩运和 我们怀疑在Pcdh介导的正确成熟下的Pcdhs的突触插入过程 匹配的突触。在完成这些目标后，我们希望更好地理解 突触发生中的细胞-细胞相互作用。

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.