FUNCTIONAL ORGANIZATION OF THE MYELIN AXOGLIAL JUNCTION

描述(摘自申请者的摘要)：尽管我们知道很多 关于紧密的髓鞘，它的组成蛋白以及它们是如何组装的，我们的 对非致密膜和细胞质通道的认识 随函附上的是极其有限的。这些航道是 髓鞘细胞，在这里与外部细胞发生分子交换 转导。在旁结节的近对置处形成的一个结构 神经胶质膜的环是轴突连接，一个非同寻常的、复杂的 其组成蛋白质的结构，除了少数例外，仍然未知。多么 这个连接的蛋白质组分相互作用，产生梯状裂隙 用薄片显微镜观察结构是一个令人着迷的问题，其 解决方案将有助于理解髓鞘细胞浆是如何 轴突表面附着有膜。作为一个相关的问题， 直接从中枢神经系统神经胶质侧发出的细胞质通道 轴突连接带几乎肯定是被固定在一起的，S他们在 通过黏附分子，PNS可能属于钙粘蛋白超家族。 我们的长期目标是了解黏附分子的生物学 在髓鞘非致密区域的介导膜相互作用 尤其是偏执狂。这是一个实现单元格的应用程序 我们已经开发了分离这些膜元素的分馏方案 从高纯度的中枢神经系统白质中，认同最伟大的 特异度和最高灵敏度的组成蛋白使用 最先进的质谱学，然后研究胶粘剂的相互作用 在显示它们的膜表面的这些蛋白质之间。

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.