BIOSYNTHESIS AND ASSEMBLY OF MYELIN MEMBRANE PROTEINS

主要髓磷脂多肽的空间排列 髓鞘膜中的磷脂双层及其与 其他信息将被确定，此结构信息将与 多肽的生物合成和组装过程 发育中的髓鞘。髓鞘转移的途径 从内质网到鞘内的蛋白质脂蛋白 少突胶质细胞的过程将通过细胞分离来研究，使用 脉冲标记技术和免疫电子显微镜。一次尝试 将被用来描述髓鞘多肽在 具有高级髓鞘组织的质膜。 重组DNA方法将被用来识别和表征基因 主要的髓鞘蛋白。髓鞘蛋白脂的一级结构 从DNA序列分析中确定的蛋白质将被解释 鉴于存在由以下标识的特定结构域 该蛋白跨膜处置的直接生物化学研究 在髓鞘和内质网膜上。DNA和DNA序列的分析 髓鞘碱性蛋白的基因组克隆将揭示这些 单个基因家族的不同成员的产物或源自 差异剪接单个基因的初级转录本 反应。克隆的髓鞘碱性蛋白cDNA将作为探针用于 确定小鼠髓鞘功能障碍的分子基础 突变体“颤栗”，它似乎在合成方面存在缺陷 中枢神经系统髓鞘碱性蛋白，并研究 在发育过程中不同组髓鞘的调节过程 蛋白质在中枢和外周神经系统中表达。

The spatial arrangement of the major myelin polypeptides with respect to the phospholipid bilayer in the myelin membrane and with respect to each other will be determined and this structural information will be related to the processes of biosynthesis and assembly of the polypeptides into the developing myelin sheath. The pathway of transfer of the myelin proteolipid protein from the endoplasmic reticulum to the ensheathing process of the oligodendrocyte will be studied by cell fractionation, using pulse labelling techniques, and by immune electron microscopy. An attempt will be made to relate the disposition of the myelin polypeptides in the plasma membrane with the higher order organization of the myelin sheath. Recombinant DNA methods will be used to identify and characterize genes for the major myelin proteins. The primary structure of the myelin proteolipid protein as determined from the DNA sequence analysis, will be interpreted in light of the existence of specific structural domains identified by direct biochemical studies of the transmembrane disposition of this protein in myelin and endoplasmic reticulum membranes. The analysis of cDNA and genomic clones for the myelin basic proteins will reveal whether these are products of different members of a single gene family or are derived from the primary transcript of a single gene by differential splicing reactions. Cloned myelin basic protein cDNAs will be employed as probes to determine the molecular basis for the defect in the mouse dysmyelinating mutant "Shiverer", which appears to be deficient in the synthesis of the central nervous system myelin basic proteins, and to investigate the regulatory processes by which during development different sets of myelin proteins are expressed in the central and peripheral nervous systems.