Elucidating the on/off switch for an essential mitotic motor

阐明重要的有丝分裂马达的开关

• 批准号: BB/H005137/1
• 负责人: Carolyn Moores
• 金额: $ 41.6万
• 依托单位: Birkbeck, University of London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FH005137%2F1
• 关键词: Elucidating; off; switch; essential; mitotic

The purpose of this research is to discover how cell multiplication is controlled and how it might be turned on and off. In the same way as our bodies have a skeleton that provides us with support and strength, the cells of our bodies have a skeleton - called the cytoskeleton - which also provides support and strength. The cytoskeleton is involved in many important aspects of the life of the cell, including cell movement, architecture and multiplication. Studying the cytoskeleton is important both so we can understand how healthy cells work, but also to understand malfunctions of the cytoskeleton in disease. My research team studies the three-dimensional structure of the cytoskeleton, because knowing what the cytoskeleton looks like contributes to our understanding of how it works in the cell. We use a very powerful microscope to take pictures of individual cytoskeleton molecules and then use computers to combine these pictures and calculate their three-dimensional shape. Our current research focuses on a part of the cytoskeleton called microtubules. These are long cylindrical structures that act like tracks around the cell and along which the cell's transporter motors travel; these motors are called kinesins and there are lots of different types. In this project, we will be studying a kinesin type-5, which is very important for accurate cell multiplication. We want to know how kinesin-5s use cellular fuel to move along microtubules and how this activity is controlled. We have had some exciting recent results from our microscopy studies and we want to know more about how this tiny, essential motor works. Previous experiments, including our own research, have suggested that kinesin-5 motors have an on-off switch that tells them when to move, but we don't understand very well how this works. The aim of our new project is to understand this switch and what controls it. This is particularly important because we know that cancer results from out-of-control cell multiplication, so we also hope that by understanding how kinesin-5 switches itself on and off, we might be able to provide more insight into how cancer can be treated.

这项研究的目的是发现细胞增殖是如何被控制的，以及它是如何开启和关闭的。就像我们的身体有一个骨架为我们提供支撑和力量一样，我们身体的细胞也有一个骨架——叫做细胞骨架——它也提供支撑和力量。细胞骨架参与细胞生命的许多重要方面，包括细胞运动、结构和增殖。研究细胞骨架很重要，不仅可以让我们了解健康细胞是如何工作的，还可以了解细胞骨架在疾病中的故障。我的研究小组研究细胞骨架的三维结构，因为知道细胞骨架的样子有助于我们理解它在细胞中的工作原理。我们用一个非常强大的显微镜来拍摄单个细胞骨架分子的照片，然后用计算机将这些照片组合起来，计算出它们的三维形状。我们目前的研究集中在细胞骨架的一部分，称为微管。它们是长圆柱形结构，就像细胞周围的轨道一样，细胞的转运体马达沿着它运动；这些马达被称为运动蛋白，有很多不同的类型。在这个项目中，我们将研究一种5型激酶，它对细胞的精确增殖非常重要。我们想知道运动蛋白5是如何利用细胞燃料沿着微管移动的，以及这种活动是如何被控制的。我们最近从显微镜研究中得到了一些令人兴奋的结果，我们想更多地了解这个微小的、基本的运动是如何工作的。以前的实验，包括我们自己的研究，已经表明，kinesin-5马达有一个开关，告诉它们何时移动，但我们不太了解它是如何工作的。我们新项目的目的是了解这个开关以及控制它的因素。这一点尤其重要，因为我们知道癌症是由失控的细胞增殖引起的，所以我们也希望通过了解驱动蛋白-5如何打开和关闭自己，我们可能能够为如何治疗癌症提供更多的见解。

项目成果

Cut7-Driven Microtubule Sliding Reverses Direction Depending on Motor Density

Cut7 驱动的微管滑动根据电机密度反转方向

• DOI: 10.1016/j.bpj.2013.11.4273
• 发表时间: 2014
• 期刊: Biophysical Journal
• 影响因子: 3.4
• 作者: Britto M

Kinesin-5 mitotic motors: Is loop5 the on/off switch?

Kinesin-5 有丝分裂马达：loop5 是开关吗？

• DOI: 10.4161/cc.9.7.11144
• 发表时间: 2010
• 期刊: Cell cycle (Georgetown, Tex.)
• 作者: Moores CA

Loop L5 Acts as a Conformational Latch in the Mitotic Kinesin Eg5

Loop L5 作为有丝分裂驱动蛋白 Eg5 中的构象锁存器

• DOI: 10.1016/j.bpj.2010.12.3096
• 发表时间: 2011
• 期刊: Biophysical Journal
• 影响因子: 3.4
• 作者: Behnke-Parks W