Structure And Function Of Cytoplasmic Motors

细胞质马达的结构和功能

• 批准号: 6548719
• 负责人: Thomas S Reese
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6548719
• 关键词: actins; axon; confocal scanning microscopy; cytoskeletal proteins; cytoskeleton; dynein ATPase; histogenesis; intracellular transport; kinesin; myosins; neuronal transport; neurons; organelles; protein structure function; squid; tissue /cell culture

Delivery to nerve terminals of cytoskeletal proteins synthesized in the cell body is crucial for growth, maintenance and regeneration of neurons. Important questions about this slow transport are by what motors and in what forms are proteins are transported. The movements of fluorescent labeled cytoskeletal proteins injected into the squid giant axon were examined by confocal microscopy. A novel finding is that there is diffusion of these proteins simultaneous with the expected energy dependent movements. Inhibiting the molecular motors: myosin, kinesin, and dynein as well as disrupting specific cytoskeletal tracts pharmacologically, or with a newly developed 2-photon lesioning technique, has begun to elucidate which motors and tracts are responsible for slow transport of axonal proteins. Binding coefficients of proteins within the transport complex are also under investigation. In addition to studying transport, supplemental work on one particular motor, myosin, has shown that it is responsible for the purse-string constriction of the axons that follows axonal transection. Because of this role, as well as its possible role in some aspects of slow transport, the myosins in the giant axon have been sequenced and characterized to produce probes for functional studies.

将细胞体中合成的细胞骨架蛋白递送到神经末梢对于神经元的生长、维持和再生至关重要。关于这种缓慢运输的重要问题是蛋白质是通过什么样的马达和以什么形式运输的。用共聚焦显微镜观察荧光标记的细胞骨架蛋白注入鱿鱼巨轴突的运动。一个新的发现是，这些蛋白质的扩散与预期的能量依赖运动同时进行。抑制分子马达：肌球蛋白、驱动蛋白和动力蛋白以及破坏特定的细胞骨架束，或者用新开发的2-光子损伤技术，已经开始阐明哪些马达和束负责轴突蛋白的缓慢运输。运输复合物内蛋白质的结合系数也正在调查中。除了研究运输之外，对一种特殊的马达肌球蛋白的补充研究表明，它负责轴突横断后轴突的荷包收缩。由于这种作用，以及它在缓慢运输的某些方面可能发挥的作用，巨大轴突中的肌球蛋白已被测序和表征，以产生用于功能研究的探针。