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.

动物、植物和真菌的所有细胞都由不同的隔室组成，每个隔室都有独特的组成和特定的功能。物质在这些隔间或细胞器之间运输，在称为囊泡的膜结合包中。这一过程被称为膜运输，是细胞和整个生物体正常运作所必需的。例如，激素、抗体、神经递质以及皮肤、软骨和骨骼的主要成分从细胞中释放出来，并与细胞表面融合，而生长因子和死细胞则从细胞表面吸收的囊泡中从血流中去除。高尔基体是细胞中的一个主要区室，它是一组扁平的膜袋，称为池，它们彼此层叠形成堆叠。高尔基体有两个主要功能：它负责修饰蛋白质和脂质上的糖链;以及将这些分子包装到运输囊泡中，以递送到细胞表面或细胞中的其他隔室。蛋白质的适当修饰和递送是至关重要的。高尔基体功能和一般膜交通的缺陷是导致许多人类疾病的原因。此外，膜运输机器的组件，包括高尔基体的组件，被某些细菌和病毒劫持，使这些病原体能够复制和/或避免被免疫系统检测到。因此，我们在分子水平上了解高尔基体的功能是很重要的。当细胞分裂时，细胞器由子细胞继承。对于高尔基体，这涉及到分裂成更小的结构，并需要修改关键的高尔基体组件。我们最近已经确定了这些组件之一的GBF 1，一种蛋白质已知是重要的膜交通在高尔基体。GBF 1在细胞分裂过程中的修饰表明它在高尔基体遗传中起重要作用。在这个项目中，我们的目标是研究如何GBF 1被修改，以及如何这种修改是重要的高尔基体和细胞作为一个整体的分裂。这将增加我们对细胞如何分裂的知识，这与包括癌症在内的许多疾病有关。我们还计划确定GBF 1是如何被招募到高尔基体的，这对于我们理解所有细胞（包括那些不分裂的细胞）中的膜交通非常重要。最后，由于GBF 1是脊髓灰质炎病毒等病毒的目标，我们的工作将为这些病毒病原体如何影响GBF 1功能提供新的见解，这将为更好地设计针对它们的治疗策略提供信息。