MOLECULAR MOTION IN DEVELOPING MUSCLE

肌肉发育中的分子运动

• 批准号: 3395628
• 负责人: DANIEL AXELROD
• 金额: $ 15.89万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-07-01 至 1988-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3395628
• 关键词: acetylcholine; cell membrane; chemical aggregate; cholinergic agents; computer graphics /printing; fluorescence; fluorescence spectrometry; membrane reconstitution /synthesis; mixed tissue /cell culture; myofibrils; myogenesis; neuromuscular function; synapses; tissue /cell culture

This project will investigate the causes, molecular mechanisms, and effects of clustering of acetylcholine receptors on developing muscle membranes. Clustering of acetylcholine receptors is a central phenomenon in both the formation of neuromuscular junctions in an embryo and in the regeneration of muscular control after an injury. Therefore, the results of this investigation will have a bearing on understanding of genetic neuromuscular defects, neuromuscular disease, and recovery after an injury to the motor system. In addition, the optical techniques (mainly fluorescence) to be employed are rather novel and powerful and should find application in a wide range of problems in cell biology and membrane function. In particular, the effect of neurotrophic factors and physical contact on the rotational mobility of acetylcholine receptors will be examined on developing rat myotubes in culture. Endogenous clusters of receptors form on these myotubes in the absence of neural influence; the locations, time, and mode of their formation will be monitored. The molecular structure of endogenous receptor clusters will be studied by observaing the effect of specifically targeted treatments and drugs on rotational mobility and by examining the codistribution of these receptors with other particular cytoplasmic, membrane, or exocellular proteins. The self-aggregating properties of acetylcholine receptors will be examined in solution and in reconstituted membranes and then compared with the size of receptor microclusters that occur in all regions of the myotube membrane. Rotational mobility of receptors on embryonic myotubes in culture will be compared to that on developing and adult synapses of rat. Lastly, clustering of receptors may affect their function, in particular their chemical kinetic rates of binding to agonists. A new fluorescence technique for measuring chemical kinetics at equilibrium in biological systems will be applied to examine this possibility and to find correlations with the kinetics of ion channel opening and closing of acetylcholine receptors.

这个项目将调查的原因，分子机制，和影响 乙酰胆碱受体聚集在发育中的肌肉膜上。 乙酰胆碱受体的聚集是这两种细胞中的中心现象。 在胚胎和再生中形成神经肌肉接头 受伤后肌肉控制的能力。 因此，这样做的结果 这项研究将有助于理解遗传性神经肌肉 缺陷、神经肌肉疾病和运动损伤后的恢复 系统 此外，光学技术（主要是荧光）， 所采用的是相当新颖和强大的，应该找到一个应用程序， 细胞生物学和膜功能的广泛问题。 特别是，神经营养因子和身体接触对 乙酰胆碱受体的旋转迁移率将在 在培养物中发育大鼠肌管。 内源性受体簇形成 在没有神经影响的情况下，这些肌管上的位置，时间， 并将监测其形成方式。 内源性受体簇的分子结构将通过 观察特异性靶向治疗和药物对 旋转流动性，并通过检查这些受体的共分布 与其他特定的细胞质、膜或细胞外蛋白质结合。 的 乙酰胆碱受体的自聚集特性将在 溶液和重构膜中，然后与 受体微簇，发生在肌管膜的所有区域。 在培养的胚胎肌管上的受体的旋转移动性将是 与发育期和成年期大鼠的突触相比。 最后，受体的聚集可能会影响它们的功能，特别是 它们与激动剂结合的化学动力学速率。 一种新的荧光 用于测量生物学中平衡时的化学动力学的技术 系统将被应用于检查这种可能性，并找到 与离子通道开放和关闭动力学的相关性 乙酰胆碱受体