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

所有来自动物、植物和真菌的细胞都由不同的隔间组成，每个隔间都有独特的组成和特定的功能。物质在这些隔室或细胞器之间以被称为囊泡的薄膜包裹的形式运输。这一过程被称为膜运输，是细胞和生物体作为一个整体正常运作所必需的。例如，荷尔蒙、抗体、神经递质以及皮肤、软骨和骨骼的主要成分通过与细胞表面融合的囊泡从细胞中释放出来，而生长因子和死亡细胞则通过从细胞表面吸收的囊泡从血液中移除。细胞中的一个主要隔室是高尔基体，这是一组扁平的膜袋，称为池子，它们相互层叠，形成堆叠。高尔基体有两个主要功能：它负责修饰存在于蛋白质和脂类上的糖链；以及将这些分子包装成运输小泡，以便运送到细胞表面或细胞内的其他隔室。蛋白质的适当修饰和传递是至关重要的。高尔基体功能的缺陷和膜的运输通常是导致许多人类疾病的原因。此外，膜运输机械的部件，包括高尔基体的部件，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。因此，重要的是我们要了解高尔基体如何在分子水平上发挥作用。当细胞分裂时，细胞器由子代细胞继承。对于高尔基体，这涉及到碎裂成更小的结构，并需要修改关键的高尔基体组件。我们最近确定了其中一个成分是GBF1，这是一种已知对高尔基体细胞膜运输起重要作用的蛋白质。GBF1在细胞分裂过程中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是如何被修饰的，以及这种修饰对高尔基体和细胞作为一个整体的分裂是如何重要的。这将增加我们对细胞如何分裂的了解，这与包括癌症在内的许多疾病有关。我们还计划确定GBF1是如何被招募到高尔基体的，这对于我们理解所有细胞的膜交通非常重要，包括那些没有分裂的细胞。最后，由于GBF1是脊髓灰质炎病毒等病毒的靶标，我们的工作将为这些病毒病原体如何影响GBF1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。

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.