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.

将细胞体合成的细胞骨架蛋白输送到神经末梢对神经元的生长、维持和再生至关重要。关于这种缓慢运输的重要问题是，蛋白质是通过什么马达和什么形式运输的。共聚焦显微镜观察注射入鱿鱼巨轴突内的荧光标记细胞骨架蛋白的运动情况。一个新的发现是，在预期的能量依赖运动的同时，这些蛋白质也在扩散。抑制分子马达：肌球蛋白、动蛋白和动力蛋白，以及从药理上或通过新开发的双光子损伤技术扰乱特定的细胞骨架束，已经开始阐明哪些马达和束是轴突蛋白运输缓慢的原因。运输复合体内蛋白质的结合系数也在研究中。除了研究运输，对一种特殊的马达肌球蛋白的补充研究表明，肌球蛋白对轴突横断后的轴突的钱袋收缩负有责任。由于这一作用，以及它可能在某些方面的缓慢运输的作用，巨大轴突中的肌球蛋白已经被测序和表征，以产生用于功能研究的探针。