Co-operating kinesins: understanding redundancy in microtubule motor systems

协作驱动蛋白：了解微管运动系统中的冗余

基本信息

批准号：
BB/G012652/1
负责人：
Viki Allan
金额：
$ 56.57万
依托单位：
University of Manchester
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2009
资助国家：
英国
起止时间：
2009 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FG012652%2F1
关键词：
Co operating kinesins understanding redundancy

项目摘要

Cells contain a system of filaments, called microtubules, that are made up of polymers of a protein call tubulin. Microtubules act as tracks within the cell for the transport of small structures from one region to another. This delivery system relies on proteins that 'walk' along microtubules, acting as minute motors. These motors can be attached to a variety of different structures in the cell, or 'cargoes', in much the same way that a railway engine can pull passenger coaches or freight wagons. We are interested in a group of related motors, called the kinesin family. Three sub-families (kinesins-1, -2 and -3) are known to drive the movement of membrane cargoes, which are tiny bags made up of lipid and protein that act as a delivery system for new material within the cell. The need for this active transport is particularly clear in nerve cells, where membrane vesicles carrying components needed for passing messages from one nerve cell to the next need to be delivered over long distances of up to a metre in our bodies. Even with this active transport system, this journey will take 2.5 days for material made in your spinal cord to be carried all the way down a single nerve cell to your big toe. If kinesins do not function properly, perhaps because they have a mutation, this leads to severe traffic jams, and is known to cause motor neuron disease. Most cells in the body are much smaller than nerve cells, however, and even though they contain kinesin-1, it is hard to see any effect if its motor activity is blocked. This could be because more than one type of motor co-operates to drive the movement of any particular cargo. We have evidence that this is the case for a particular cellular membrane structure, the Golgi apparatus. We will test the role of three types of kinesin motors in the movement of these membranes, and also in the transport of the tumour suppressor protein Adenomatous Polyposis Coli protein (APC). We will also establish how kinesin-1 can bind to APC and transport it to the edge of the cell. This work will define how motors work together to transport cargoes.

细胞包含一个由蛋白质称为小管蛋白的聚合物组成的细丝系统，称为微管。微管充当细胞内的轨道，用于将小结构从一个区域传输到另一个区域。该输送系统依赖于沿着微管“行走”的蛋白质，用作微型电机。这些电动机可以连接到牢房或“货物”中的各种不同结构上，就像铁路发动机可以拉动乘客教练或货车一样。我们对一组称为“动机家族”的相关电动机感兴趣。已知三个亚型含量（驱动素1，-2和-3）可以驱动膜货物的运动，膜货物的运动是由脂质和蛋白质组成的微小袋子，可作为细胞内新材料的递送系统。在神经细胞中，对这种主动传输的需求特别明显，在神经细胞中，将消息从一个神经细胞传递到下一个需要的膜囊泡中，需要在我们体内长达一米的长距离内传递。即使有了这种主动的运输系统，这一旅程仍需要2.5天的时间才能使您的脊髓制成的材料一直沿着一个神经细胞沿着一个神经细胞延伸到您的大脚趾。如果驱动蛋白的功能无法正常工作，也许是因为它们具有突变，这会导致严重的交通拥堵，并且众所周知会引起运动神经元疾病。但是，体内的大多数细胞都比神经细胞小得多，即使它们包含驱动蛋白1，也很难看到其运动活性被阻断。这可能是因为多种类型的电动机合作能够驱动任何特定货物的移动。我们有证据表明，特定的细胞膜结构是高尔基体设备。我们将测试三种类型的驱动蛋白电动机在这些膜运动中的作用，以及在肿瘤抑制蛋白腺瘤息肉蛋白（APC）中的运输中。我们还将确定运动蛋白-1如何与APC结合并将其运输到细胞的边缘。这项工作将定义电动机如何共同运输货物。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Dynein light intermediate chains maintain spindle bipolarity by functioning in centriole cohesion.

DOI：
10.1083/jcb.201408025
发表时间：
2014-11-24
期刊：
The Journal of cell biology
影响因子：
0
作者：
Jones LA;Villemant C;Starborg T;Salter A;Goddard G;Ruane P;Woodman PG;Papalopulu N;Woolner S;Allan VJ
通讯作者：
Allan VJ

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