AXONAL REGULATION OF MYELIN PROTEIN SYNTHESIS

了解施旺氏调节中涉及的过程 细胞（SC）表型将大大有助于诊断和最终 治疗某些髓鞘形成障碍的周围神经病。 它 有充分的证据表明，神经元轴突影响许多方面， 供应链行为，包括供应链实现成熟， 髓鞘形成表型 现在看来，轴突接触可以 启动主要髓鞘糖蛋白PO的生物合成， 缺乏活跃的髓鞘形成，这表明 髓鞘蛋白质合成和髓鞘组装是不同的事件 独立监管。 本提案中提出的研究 目的是了解 轴突触发SC合成髓鞘蛋白， 存在活跃的髓鞘形成。 很难分析 用来源于以下的SC诱导髓鞘蛋白表达： 髓鞘形成神经，因为这样的细胞继续表达PO（和 可能是其他髓鞘蛋白）。 为了缓解这一问题，来自颈交感干的SC (CST SC）已被部分表征，并显示不 在体内或生长后合成可观水平PO 在文化中。 这些细胞将被进一步表征并用于 解决髓鞘蛋白合成的调节。 实验 建议：1）确定和比较 在非神经细胞中髓鞘蛋白PO、MAG和MBP的表达， 髓鞘生成和髓鞘生成背根神经节（DRG）/内源性 SC培养物。 这将揭示轴突是否足以 诱导除PO以外其它髓鞘蛋白的合成，以及 表明在活性期间这些蛋白质的上调程度 髓鞘形成; 2）定量PO、MAG和MBP的水平 在成年CST SC的生物合成，以确定是否表达 后两种髓鞘蛋白的抑制程度相同 作为PO; 3）确定髓鞘蛋白质的合成水平 CST SC接种到培养基中的DRG神经突上后， 能够和不能支持髓鞘形成; 4） 检查DRG神经突培养物的信号性质 触发髓鞘蛋白的表达。 CST SC将 用于帮助分析此类组分; 5）开始 任何髓磷脂的初始生物化学表征和分离 鉴定的蛋白诱导分子。 描述的研究 应该大大增加知识的身体处理 髓鞘蛋白的表达，以及所用的培养系统 将在未来的研究解决SC表型变化有用。

Understanding the processes involved in the regulation of Schwann cell (SC) phenotype will greatly aid in the diagnosis and ultimate treatment of certain dysmyelinating peripheral neuropathies. It is well documented that neuronal axons influence many aspects of SC behavior, including the ability of SCs to achieve a mature, myelinating phenotype. It now appears that axonal contact can initiate the biosynthesis of the major myelin glycoprotein, PO, in the absence of active myelination, suggesting that the processes of myelin protein synthesis and myelin assembly are distinct events regulated independently. The studies presented in this proposal are aimed at obtaining an understanding of the mechanism whereby axons trigger SCs to synthesize myelin proteins in the absence or presence of active myelination. It is difficult to assay for the induction of myelin protein expression with SCs derived from myelinating nerve, as such cells continue to express PO (and perhaps other myelin proteins) in the absence of axonal influence. To alleviate this problem, SCs from the cervical sympathetic trunk (CST SCs) have been partially characterized and shown not to synthesize appreciable levels of PO either in vivo or after growth in culture. These cells will be characterized further and used to address the regulation of myelin protein synthesis. Experiments are proposed that will: 1) determine and compare the level of expression of the myelin proteins PO, MAG, and MBPs in non- myelinating and myelinating dorsal root ganglia (DRG)/endogenous SC cultures. This will reveal whether axons are sufficient to induce synthesis of other myelin proteins besides PO, as well as indicate the degree of upregulation of such proteins during active myelination; 2) quantitate the levels of PO, MAG, and MBPs biosynthesis in adult CST SCs to ascertain whether the expression of the latter two myelin proteins are suppressed to the same extent as PO; 3) determine the levels of synthesis of the myelin proteins by CST SCs after they have been seeded onto, DRG neurites in media that are capable and incapable of supporting myelination; 4) examine the DRG neurite cultures for the nature of the signal(s) triggering expression of myelin proteins. The CST SCs will be employed to aid in the assaying of such a component(s); 5) begin initial biochemical characterization and isolation of any myelin protein induction molecule(s) identified. The studies described should greatly increase the body of knowledge dealing with the expression of myelin proteins, and the culture systems employed will be useful in future studies addressing SC phenotypic changes.