Mechanism & Control of Brain Microtubule Dynamics

机制

• 批准号: 6639354
• 负责人: LESLIE WILSON
• 金额: $ 32.94万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA BARBARA
• 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 2005-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6639354
• 关键词: brain cell; cell component structure /function; chemical association; chemical kinetics; chemical stability; fluorescence microscopy; gene mutation; growth cones; guanine nucleotide exchange factors; guanosine triphosphate; intermolecular interaction; intravital microscopy; microinjections; microtubules; molecular dynamics; molecular genetics; neurons; phosphorylation; protein isoforms; protein metabolism; protein reconstitution; protein structure function; radiotracer; tau proteins; tissue /cell culture; tubulin

DESCRIPTION (provided by applicant): Microtubules (MTs), tube-shaped polymers composed of ab tubulin heterodimers and a diverse array of MT-associated proteins (MAPs), are critical for the development, structural organization, stability, and functions, of the axonal and dendntic processes of neurons. MTs are not simple equilibrium polymers. Guanosine-5'-triphosphate is irreversibly hydrolyzed to guanosine-5'-diphosphate and orthophosphate during tubulin addition to the MTs, which creates two unique dynamic behaviors, treadmilling and dynamic instability. These behaviors are critical for MT function in cells, and are finely regulated. Both dynamic instability and treadmilling are intrinsic properties of the tubulin backbone of MTs, while MAPs acting at the MT surfaces and ends control the dynamics. One major goal is to elucidate the mechanisms responsible for the MT's unique dynamic behaviors. A second major goal is to determine how important neuronal MAPs regulate dynamics. These studies will involve high-resolution video microscopy and radiolabeled guanine-nucleotide exchange strategies. Studies will focus on the dynamics of reconstituted brain MTs and specific neuronal MAPs in vitro, and on MT dynamics in living neuronal and non-neuronal cells. A main focus will be on the tau proteins and mutated forms of tau, which are involved in Alzheimer's disease and are causally linked to frontotemporal dementias (FTDP-17) in humans.

描述（由申请人提供）：