BIOSYNTHESIS AND ASSEMBLY OF MYELIN MEMBRANE PROTEINS

主要髓鞘多肽的空间排列相对于 髓鞘膜中的磷脂双层， 其他将被确定，并且该结构信息将与 多肽的生物合成和组装成 正在发育的髓鞘。 髓磷脂的转运途径 从内质网到成鞘的蛋白脂质蛋白质 少突胶质细胞的过程将通过细胞分级来研究，使用 脉冲标记技术和免疫电子显微镜。 试图 将涉及髓鞘多肽的处置， 质膜与髓鞘的高级组织。 重组DNA方法将用于鉴定和表征基因， 主要的髓磷脂蛋白。 髓鞘蛋白脂质的一级结构 将解释从DNA序列分析确定的蛋白质 根据存在的特定结构域， 这种蛋白质跨膜分布的直接生物化学研究 在髓鞘和内质网膜中。 cDNA分析和 髓鞘碱性蛋白的基因组克隆将揭示这些蛋白是否是 单个基因家族的不同成员的产物或来自 通过差异剪接单个基因的初级转录物 反应. 克隆的髓鞘碱性蛋白cDNA将用作探针， 确定小鼠髓鞘形成障碍缺陷的分子基础 突变体“Shiverer”，这似乎是在合成缺陷的 中枢神经系统髓鞘碱性蛋白，并探讨其在中枢神经系统中的作用。 在发育过程中， 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.