REGULATION OF NEURAL CELL ADHESION MOLECULE IN MUSCLE

这项研究的长期目标是了解 调节神经细胞黏附分子(NCAM)的是肌肉 发育过程中的变化及其细胞机制的影响 NCAM修改。希望这一知识将进一步 我们对NCAM的分子机制的理解 介导细胞黏附，因为目前还没有确切的分子 模型已存在。这些问题将通过两种类型的 学习。 首先，将通过生物合成来研究NCAM的生物合成 放射性标记培养的鸡肌管。周转时间，周转率 将检查聚唾液酸化、硫酸盐化和磷酸化。一个 与早期关于神经NCAM生物合成的研究相比， 证明了这两种多肽是相同的修饰 可能具有重要功能的组织。 第二，将考察三类监管因素 因为它们在肌管培养中调节NCAM的能力。1) 将测试影响肌肉功能活动的条件 他们是否有能力改变总的NCAM水平(由 酶联免疫吸附试验)、多肽大小和多唾液酸化(如在十二烷基硫酸钠- 页)。神经元在体内的调节下调NCAM 多肽合成和聚唾液酸化。因此，肌管培养 提供了一个系统，在该系统中可以隔离测试各种因素 它们模拟神经元调节的能力2)对NCAM的调节 类固醇激素将通过类似的治疗进行检查 使用地塞米松和多种类固醇进行培养 几天。3)细胞内第二信使的参与 将探索NCAM调控的调控机制 通过研究影响几种激酶的因素，如循环 核苷酸和二酰甘油。NCAM将被量化并 长期治疗后研究多唾液酸化，而 磷酸化将在较短的处理后进行研究。 NCAM法规在发展中似乎很重要 神经肌肉连接，在成人疾病中改变，如 多发性肌炎、Duchenne和Becker肌营养不良 肩胛骨和四肢腰带营养不良。了解ITS 监管将有助于开发一种精确的分子模型 NCAM功能，这可能解释其参与 退行性肌肉疾病，以及它在 组织发生学。

The long term goals of this study are to understand how the regulation of the neural cell adhesion molecule (NCAM) is muscle changes during development and what cellular mechanisms affect NCAM modification. It is hoped that this knowledge will further our understanding of the molecular mechanism by which NCAM mediates cell adhesion, since at present no precise molecular model exists. These questions will be addressed by two types of studies. First, NCAM biosynthesis will be studied by biosynthetic radiolabelling cultured chick myotubes. Turnover time, rate of polysialation, sulfation and phosphorylation will be examined. A comparison with earlier studies on neural NCAM biosynthesis will establish it the polypeptides are identically modified in the two tissues which could be of functional importance. Second, regulatory factors of three categories will be examined for their ability to regulate NCAM in myotube culture. 1) Conditions that affect muscle functional activity will be tested for their ability to alter total NCAM levels (as determined by ELISA), polypeptide size and polysialation (as determined on SDS- PAGE). Neuronal regulation in vivo down-regulated NCAM polypeptide synthesis and polysialation. Hence myotube culture provides a system where factors can be tested in isolation for their ability to mimic neuronal regulation 2) Regulation of NCAM by steroid hormones will be similarly examined by treating cultures with dexamethasone and a variety of steroids for several days. 3) The involvement of second messengers in the cellular control mechanism mediating NCAM regulation will be explored by studying factors affecting several kinases, such as cyclic nucleotides and diacylglycerol. NCAM will be quantified and polysialation studied after prolonged treatment, while phosphorylation will be studied after shorter treatments. NCAM regulation appears to be important in the development of neuromuscular junction and is altered in adult diseases such as polymyositis, Duchenne and Becker muscular dystrophies, and tascio-scapular and limb girdle dystrophies. Understanding its regulation will assist in developing a precise molecular model of NCAM function which may explain its involvement in degenerative muscle diseases, as well its presumed role in histogenesis.