FUNCTIONAL ORGANIZATION OF THE MYELIN AXOGLIAL JUNCTION

描述（来自申请人的摘要）：虽然我们知道很多 关于紧密髓鞘，其组成蛋白质以及它们如何组装，我们的 非致密膜和细胞质通道的知识， 封闭是非常有限的。这些渠道是“至关重要的地区”的 髓鞘形成细胞，在那里分子交换发生与外部 转导结旁核紧贴处形成一个结构 神经胶质膜的环是轴胶质连接，一个非凡的，复杂的 其组成蛋白质的结构，除了少数例外，仍然未知。如何 这个连接处的蛋白质成分相互作用， 用薄片显微镜观察结构是一个迷人的问题， 分辨率将产生对髓鞘形成细胞浆如何 膜附着于轴突表面。作为一个相关的问题， 直接从CNS神经胶质侧发出的细胞质通道 轴舌结合带几乎可以肯定是在寄存器中， PNS由粘附分子组成，可能属于钙粘蛋白超家族。 我们的长期目标是了解粘附分子的生物学， 介导髓鞘非致密区域的膜相互作用， 特别是在paranodes。这是一个应用程序， 我们已经开发了分离这些膜元件的分馏方案， 从中枢神经系统白色物质中提取，纯度高， 特异性和最高灵敏度的组分蛋白质使用 最先进的质谱分析，然后研究粘附相互作用 这些蛋白质在它们展示的膜表面之间。

DESCRIPTION (From the applicant's abstract): Although we know a great deal about compact myelin, its component proteins and how they are assembled, our knowledge of the non-compacted membranes and the cytoplasmic channels they enclose is exceedingly limited. These channels are the "vital zones" of the myelinating cell, where molecular interchanges take place with the external transduction. One structure formed at the close apposition of the paranodal loops of glial membrane is the axoglial junction, an extraordinary, complicated structure whose component proteins, with a few exceptions, remain unknown. How this junction's protein components interact to generate the ladder-like cleft structure visualized by thin section microscopy is a fascinating problem, whose resolution will yield an understanding of how the myelinating cell plasma membrane is attached to the axonal surface. As a related problem, the cytoplasmic channels immediately emanating from the glial side of the CNS axoglial junctional ribbon are almost certainly held in register, s they are in the PNS, by adhesion molecules, possible of the cadherin super family. Our long range goal is to understand the biology of the adhesion molecules that mediate membrane interactions in the non-compact regions of myelin, and in particular at the paranodes. This is an application to implement a cell fractionation scheme that we have developed to isolate these membrane elements from the CNS white matter with high purity, identify with the greatest specificity and highest sensitivity the component proteins using the state-of-the-art mass spectrometry, and then study the adhesive interactions between these proteins at the membrane surfaces on which they are displayed.