MOLECULAR MOTION IN DEVELOPING MUSCLE

肌肉发育中的分子运动

• 批准号: 3395631
• 负责人: DANIEL AXELROD
• 金额: $ 11.44万
• 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/3395631
• 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.

本项目将研究其原因、分子机制和影响。 乙酰胆碱受体在发育中的肌膜上的聚集。 乙酰胆碱受体的聚集是两种疾病的中心现象 胚胎和再生过程中神经肌肉接头的形成 受伤后的肌肉控制力。因此，这一结果 研究将关系到对遗传神经肌肉的理解 运动损伤后的缺陷、神经肌肉疾病和康复 系统。此外，光学技术(主要是荧光)将被 Employee相当新颖和强大，应该在 细胞生物学和膜功能方面的广泛问题。 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 在培养条件下发育大鼠肌管。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， 并将监测它们的形成方式。 内源性受体簇的分子结构将通过 观察特定靶向治疗和药物治疗的效果 旋转迁移率和通过检查这些受体的共同分布 与其他特定的细胞质、膜或细胞外蛋白结合。这个 乙酰胆碱受体的自聚集特性将在 溶液和重组膜中，然后与大小的 受体微簇出现在肌管膜的所有区域。 胚胎肌管上受体在培养中的旋转迁移率 与发育中的大鼠和成年大鼠的突触相比。 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 生物平衡状态下的化学动力学测量技术 将应用系统来检查这种可能性，并找出 离子通道开闭动力学的关联性 乙酰胆碱受体。