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（由应用提供）：动态微管（MT）的调节对于细胞分裂，细胞迁移，细胞极性，有机运动和核定位至关重要。了解MT调节的配置机制与人类生物学高度相关，以及癌症，神经元疾病和伤口愈合等疾病。在这笔赠款中，我们旨在通过研究MT加最终跟踪蛋白（+TIPS）来阐明负责MT调节的基本管理机制。这些蛋白质覆盖MT Plus End并控制这些聚合物的组装，稳定性和拆卸。通常，这些蛋白质如何共同起作用以在体内调节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，使用裂变酵母菌型糖果pombe作为一种可拖动的简单模型系统。 XMAP215/ALP14 +TIPS家族已成为最重要的 +尖端之一。这些微管蛋白结合蛋白充当MT聚合酶，在生长MT的末端添加微管蛋白。我们的初步结果表明，它在MT成核和拆卸中具有其他功能。我们的具体目的是：1）定义ALP14如何与伽马细胞蛋白复合物一起使用MT成核； 2）确定ALP14和Kinesin-8 KLP5/6如何调节MTS的拆卸； 3）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。