Regulation of Microtubule Dynamics

微管动力学的调节

基本信息

批准号：
9316669
负责人：
Fred Chang
金额：
$ 38.98万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-03-01 至 2019-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9316669
关键词：
Anaphase Behavior Binding Binding Proteins Biological Models Capsid Proteins Cell Polarity Cell Shape Cell division Cell physiology Cells Complex Crystallization Cytoskeleton DNA Data Databases Defect Dimerization Disease Employee Strikes Evolution Family Fission Yeast Foundations Gamma-Tubulin Ring Goals Grant Growth Human Biology In Vitro Kinesin Malignant Neoplasms Mammalian Cell Microtubules Mitotic spindle Molecular Mutation Analysis Neurons Nuclear Phenotype Plus End of the Microtubule Polymerase Polymers Positioning Attribute Process Production Proteins Regulation Role Signal Transduction Structure Testing Time Tube Tubulin Work Wound Healing base cancer stem cell cell motility dimer gamma Tubulin human disease in vivo insight mutant nervous system disorder novel organelle movement protein function public health relevance trafficking

项目摘要

DESCRIPTION (provided by applicant): Regulation of dynamic microtubules (MTs) is critical for cellular processes such as cell division, cell migration, cell polarity, organelle movements and nuclear positioning. Understanding conserved mechanisms of MT regulation are highly relevant to human biology and diseases such as cancer, neuronal diseases and wound healing. In this grant, we aim to elucidate fundamental conserved mechanisms responsible for MT regulation by studying MT plus end tracking proteins (+TIPs). These proteins coat the MT plus end and control the assembly, stability and disassembly of these polymers. In general, how these proteins work collectively to regulate MT dynamics in vivo is a pressing question in this active field. We study MT regulation using in vivo and in vitro approaches, using the fission yeast Schizosaccharomyces pombe as a tractable, simple model system. The XMAP215/Alp14 family of +TIPs is emerging as one of the most important of the +TIPs. These tubulin-binding proteins function as MT polymerases that add tubulin onto the ends of growing MT. Our preliminary results suggest that it has additional functions in MT nucleation and disassembly. Our specific aims are: 1) To define how Alp14 works with gamma tubulin complex for MT nucleation; 2) To determine how Alp14 and the kinesin-8 Klp5/6 regulate the disassembly of MTs; 3) To elucidate the molecular mechanisms of how XMAP215/Alp14 proteins interact with tubulin to regulate MT dynamics.

描述（由申请人提供）：动态微管 (MT) 的调节对于细胞分裂、细胞迁移、细胞极性、细胞器运动和核定位等细胞过程至关重要。了解 MT 调节的保守机制与人类生物学和疾病高度相关。在这项资助中，我们的目标是通过研究 MT plus 末端跟踪蛋白（+TIP）来阐明负责 MT 调节的基本保守机制。一般来说，这些蛋白质如何共同调节体内 MT 动力学是这个活跃领域的一个紧迫问题，我们使用体内和体外方法研究 MT 调节。裂殖酵母裂殖酵母作为一种易处理、简单的模型系统，+TIP 的 XMAP215/Alp14 家族正在成为最重要的 +TIP 之一。微管蛋白结合蛋白起到 MT 聚合酶的作用，将微管蛋白添加到正在生长的 MT 末端。我们的初步结果表明，它在 MT 成核和分解中具有其他功能：1) 确定 Alp14 如何与 γ 微管蛋白复合物一起发挥作用。 MT 成核；2) 确定 Alp14 和驱动蛋白-8 Klp5/6 如何调节 MT 的分解；阐明 XMAP215/Alp14 蛋白如何与微管蛋白相互作用以调节 MT 动力学的分子机制。