The role of microtubule motor proteins in cargo sorting

人体中所有细胞的正确功能都取决于它们内部被划分为离散的隔间这一事实。这确保了生化反应能够特异性和高效地发生（如新蛋白质的合成，它们的修饰和加工）。这也意味着细胞需要一种方式来在不同的区室之间进行交流，并在它们之间运输物质（例如，一种新合成的激素进入其最终状态的顺序处理，就像胰岛素一样）。我们研究材料在隔室之间移动的过程，以及这些在隔室之间移动的载体被运输的机制。关键问题集中在确保各部门保持不同的机制上。舱室身份？)以及具体货物的运输方式？被选中用于运输，但其他货物被排除或移除，如果错误合并。我们的假设是建立在我们自己和其他人的工作的坚实基础上的，即这些结构内货物的分类与驱动它们运动的马达内在地联系在一起。存在特定的马达使这些载体囊泡向一个方向或另一个方向移动。我们建议（并有证据表明）电机与不同的货物相耦合。使用极性相反的马达对不同的货物施力，会将这些货物在一个结构中分离成离散的区域。因此，我们将产生一个依赖于电机的货物分类，并将其定向到一个方向而不是另一个方向。我们建议利用先进的显微镜技术在活细胞中测试这些想法，并将载体的运动和形态与这些分选事件联系起来。这些实验将使我们清楚地了解货物分拣发生的机制。在现有非常强大的合作基础上，我们希望整合两种膜运输方法，以提供全面的分析，并使用这种协同方法，以提供对工作中的一般机制的更充分的理解。这种方法可能对正常和疾病状态下的膜运输机制具有重要意义。

The correct function of all cells in the human body depends on the fact that they are internally divided in to discrete compartments. This ensures that biochemical reactions can occur specifically and efficiently (such as the synthesis of new proteins, their modification and processing) . It also means that the cell requires a means to communicate between compartments and to transport material between them (for example for sequential processing of a newly synthesized hormone in to its final state as occurs for insulin). We study the process by which material is moved between compartments and the mechanisms by which these carriers moving between them are transported. Key questions are centred on the mechanisms that ensure that compartments remain distinct (?compartment identity?) as well as the way in which specific ?cargo? is selected for transport but other cargo excluded or removed if incorporated by mistake. Our hypothesis, which is built on very solid foundations from our own work as well as that of others, is that the sorting of cargo within these structures is inherently linked to the motors that drive their movement. Specific motors exist to move these carrier vesicles in one direction or another. We propose (and have evidence that) motors are coupled to distinct cargoes. Applying force to different cargos using motors of opposing polarity would segregate these cargoes within a structure in to discrete domains. Thus, we would generate a motor-dependent sortig of cargo to be directed in one direction versus another. We propose to use our experience of advanced microscopy to test these ideas in living cells and to correlate both the movement and morphology of carriers with these sorting events. These experiments should lead to a clear understanding of the mechanism by which cargo sorting occurs. Building on a very strong existing collaboration, we wish to integrate two membrane trafficking approaches to provide a comprehensive analysis and to use this synergistic approach to provide a fuller understanding of the general mechanisms at work. This approach is likely to have significant implications for the mechanisms of membrane trafficking in both normal and disease states.