Mitotic regulation of the Golgi apparatus- the role of the ARF nucleotide exchange factor GBF1

高尔基体的有丝分裂调节——ARF核苷酸交换因子GBF1的作用

• 批准号: BB/F005628/1
• 负责人: Martin Lowe
• 金额: $ 36.76万
• 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: 2008
• 资助国家: 英国
• 起止时间: 2008 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FF005628%2F1
• 关键词: Mitotic; regulation; Golgi; apparatus; role

All cells from animals, plants and fungi are made up of different compartments, each with a unique composition and specific functions. Material is transported between these many of these compartments, or organelles, in membrane-bound packets called vesicles. This process, referred to as membrane traffic, is required for the correct functioning of cells, and organisms as a whole. For example hormones, antibodies, neurotransmitters, and the major components of skin, cartilage and bone are released from cells in vesicles that fuse with the cell surface, while growth factors and dead cells are removed from the bloodstream in vesicles that are taken up from the cell surface. One of the major compartments in cells is the Golgi apparatus, a collection of flattened membrane sacks called cisternae that are layered on top of each other to form stacks. The Golgi apparatus has two major functions: it is responsible for modifying sugar chains present on proteins and lipids; and the packaging of these molecules into transport vesicles for delivery to the cell surface or other compartments in the cell. Proper modification and delivery of proteins is of fundamental importance. Defects in Golgi function, and membrane traffic in general, are responsible for a number of human diseases. Furthermore, components of the membrane traffic machinery, including those at the Golgi apparatus, are hijacked by certain bacteria and viruses, allowing these pathogens to replicate and/or avoid detection by the immune system. It is therefore important we understand how the Golgi apparatus functions at the molecular level. When cells divide organelles are inherited by the daughter cells. For the Golgi apparatus, this involves fragmentation into smaller structures, and requires the modification of key Golgi components. We have recently identified one of these components as GBF1, a protein known to be important for membrane traffic at the Golgi apparatus. The modification of GBF1 during cell division suggests it plays an important role in Golgi inheritance. In this project we aim to investigate how GBF1 is modified, and how this modification is important for the division of the Golgi apparatus and cells as a whole. This will increase our knowledge of how cells divide, which is relevant to many diseases including cancer. We also plan to determine how GBF1 is recruited to the Golgi, which is important for our understanding of membrane traffic in all cells, including those that are not dividing. Finally, since GBF1 is targeted by viruses such as poliovirus, our work will provide new insights into how these viral pathogens influence GBF1 function, which will inform better design of therapeutic strategies against them.

来自动物，植物和真菌的所有细胞均由不同的隔室组成，每个隔室具有独特的组成和特定功能。在称为囊泡的膜结合的小包中，在这些隔室或细胞器中的许多隔室之间运输材料。此过程被称为膜流量，需要细胞的正确功能和整个生物。例如，激素，抗体，神经递质以及皮肤，软骨和骨骼的主要成分是从囊泡中与细胞表面融合的细胞中释放的，而生长因子和死细胞则从细胞表面取走的囊泡中的血液中除去。细胞中的主要隔室之一是高尔基体设备，这是一个称为Cisternae的扁平膜麻袋，它们彼此层面上层面以形成堆栈。高尔基体具有两个主要功能：它负责修饰蛋白质和脂质上存在的糖链；这些分子将这些分子包装到传输囊泡中，以递送到细胞表面或细胞中的其他隔室。蛋白质的适当修改和递送至关重要。高尔基体功能的缺陷以及一般的膜流量导致了许多人类疾病。此外，膜交通机械的组件，包括高尔基体的膜交通机制，被某些细菌和病毒劫持，使这些病原体可以复制和/或避免被免疫系统检测。因此，重要的是我们了解高尔基体如何在分子水平上起作用。当细胞分裂细胞器时，由子细胞遗传。对于高尔基体，这涉及碎片化成较小的结构，并且需要修改关键的高尔基分量。我们最近将这些成分之一确定为GBF1，这是一种对高尔基体膜流量很重要的蛋白质。细胞分裂过程中GBF1的修饰表明它在高尔基体遗传中起着重要作用。在这个项目中，我们旨在研究GBF1如何修改，以及这种修饰对于Golgi设备和整个细胞的划分至关重要。这将增加我们对细胞分裂的了解，这与包括癌症在内的许多疾病有关。我们还计划确定如何将GBF1招募到高尔基体，这对于我们对所有细胞中膜流量的理解非常重要，包括那些没有分裂的细胞。最后，由于GBF1是诸如脊髓灰质炎病毒之类的病毒的靶向，因此我们的工作将提供有关这些病毒病原体如何影响GBF1功能的新见解，这将为他们更好地设计针对它们的治疗策略。