权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

MICROTUBULE-ASSOCIATED COUPLERS AND AXONAL TRANSPORT

微管相关耦合器和轴突运输

基本信息

批准号：
3449791
负责人：
ROBERT G NAGELE
金额：
$ 4.84万
依托单位：
UNIV OF MED/DENT NJ-SCH OSTEOPATHIC MED
依托单位国家：
美国
项目类别：
财政年份：
1986
资助国家：
美国
起止时间：
1986-04-01 至 1989-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3449791
关键词：
actins axon chick embryo cinemicrography cytoskeleton electron microscopy histochemistry /cytochemistry immunochemistry laboratory mouse laboratory rat microfilaments microtubules myosins neurofilament neurogenesis neuronal transport organelles tissue /cell culture

项目摘要

The axonal transport system is known to play a key role in maintaining the structural and functional integrity of axons. A defective axonal transport system may contribute to the etiology of certain nerve degenerative diseases and peripheral neuropathies associated with exposure to neurotoxic chemicals. Although much information on the transport of axonal constituents (especially proteins) has been obtained using radioactive tracer techniques, the structural and molecular bases axonal transport remain elusive. Recently, we reported the discovery of a microtubule (MT)-associated "coupler" in axons. This structure links MTs to other cytoskeletal components as well as to various types of membrane-bound organelles (MBOs) and redistributes so as to remain associated with MTs in axons treated with B,B'-iminodipropionitrile (IDPN). These findings along with those of previous studies suggest that couplers are involved in the generation of motive forces for fast axonal transport. The main objectives of the proposed study are to further our understanding of (1) the structure, composition and function of couplers in axons and (2) the relationship of couplers to cytoskeletal elements during nerve growth and axonal transport. The following major approaches are planned: (1) More rapid and improved fixation methods will be used to reveal structures that participate in axonal transport. (2) Segregation of MTs and neurofilaments induced with B,B"-iminodipropionitrile will be used as a model system to study the individual roles of MTs, NFs and couplers in nerve growth and axonal transport. (3) Correlated time-lapse cinemicrography and electron microscopy will be used to relate directly variations in the nerve growth rate with changes in the number and distribution of couplers and the organizational state of the axonal cytoskeleton. (4) Immunocytochemical techniques will be used to examine the composition of couplers. The studies will help elucidate the structural and molecular bases of nerve growth and axonal transport which, in turn, will shed new light on the underlying causes of axonopathies associated with certain neurotoxic and nerve degenerative diseases which may be due, at least in part, to a defective axonal transport system.

已知轴突运输系统在维持神经元的功能中起关键作用。轴突的结构和功能完整性。轴突运输缺陷系统可能有助于某些神经退行性疾病的病因与接触神经毒素有关的疾病和周围神经病化学品虽然关于轴突运输的许多信息成分（特别是蛋白质）已获得使用放射性示踪技术，轴突运输的结构和分子基础仍然难以捉摸最近，我们报道了一个微管（MT）相关的发现，轴突中的“耦合器”。这种结构将MT与其他细胞骨架连接起来，成分以及各种类型的膜结合细胞器（MBO）并重新分布，以保持与用 B，B '-亚氨基二丙腈（IDPN）。这些发现沿着先前的研究表明，成色剂参与了快速轴突运输的动力。的主要目标建议的研究是为了进一步了解（1）结构，轴突中耦合剂的组成和功能;（2）在神经生长和轴突生长过程中与细胞骨架元素的耦合剂运输计划采取以下主要办法：（1）更迅速和将使用改进的固定方法来揭示参与轴突运输。 (2)MT和神经丝的分离用B诱导的，B”-亚氨基二丙腈将用作模型系统，研究MT、NF和耦合剂在神经生长中的各自作用，轴突运输 (3)相关延时电影显微摄影和电子显微镜将用于直接关联神经生长的变化速率随耦合器数量和分布的变化而变化，轴突细胞骨架的组织状态。 (4)免疫细胞技术将被用来检查成色剂的组成。这些研究将有助于阐明神经的结构和分子基础生长和轴突运输，这反过来将揭示新的光与某些神经毒性和神经退行性疾病，其可能是由于，至少部分，轴突运输系统缺陷