AXONAL REGULATION OF MYELIN PROTEIN SYNTHESIS

了解参与调节Schwann的过程 细胞(SC)的表型将极大地帮助诊断和最终 某些髓鞘障碍周围神经病的治疗。它 有充分的证据表明神经元轴突在许多方面影响 SC行为，包括SC实现成熟的能力， 髓鞘表型。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 没有活跃的髓鞘形成，这表明 髓鞘蛋白合成和髓鞘组装是两个不同的事件 独立监管。这项提案中提出的研究 的目的是为了了解 轴突在缺失或缺失的情况下触发干细胞合成髓鞘蛋白 存在活跃的髓鞘形成。很难对其进行检测 骨髓间充质干细胞诱导髓鞘蛋白表达 髓鞘神经，因为这类细胞继续表达PO(和 可能是其他髓鞘蛋白)，在没有轴突影响的情况下。 为了缓解这一问题，来自颈部交感神经干的干细胞 (CST SC)已部分表征，并显示不是 在体内或生长后合成可察觉的PO水平 在文化上。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问题。实验 提出将：1)确定和比较 髓鞘蛋白PO、MAG和MBPS在非淋巴组织中的表达 髓鞘和髓鞘背根神经节(DRG)/内源性 SC文化。这将揭示轴突是否足以 诱导PO以外的其他髓鞘蛋白的合成，以及 表明这些蛋白质在活动过程中上调的程度 髓鞘形成；2)定量测定PO、MAG和MBPS水平 在成体CST SCs中的生物合成以确定其表达是否 在后两种髓鞘蛋白中，抑制程度相同 AS PO；3)测定髓鞘蛋白的合成水平 由CST SCs接种到介质中的DRG轴突上 有能力和无能力支持髓鞘形成的；4) 检查背根神经节神经突起培养以了解信号的性质(S) 触发髓鞘蛋白的表达。CST SC将是 受雇协助分析这种成分(S)；5)开始 任何髓鞘的初步生化特性和分离 蛋白质诱导分子(S)鉴定。这些研究描述了 应该大大增加处理的知识主体 髓鞘蛋白的表达和所采用的培养系统 将在未来解决SC表型变化的研究中有用。

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.