Dissecting the roles of ZFPL1 and GMAP210 in Golgi biogenesis and membrane traffic

剖析 ZFPL1 和 GMAP210 在高尔基体生物发生和膜运输中的作用

• 批准号: BB/I007717/1
• 负责人: Martin Lowe
• 金额: $ 43.07万
• 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: 2011
• 资助国家: 英国
• 起止时间: 2011 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FI007717%2F1
• 关键词: Dissecting; roles; ZFPL1; GMAP210; Golgi

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 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. All membrane traffic steps involve a process called tethering, which is the initial attachment of the transport carrier to its destination compartment. There are many tethering factors in cells, including a family of related tethering proteins at the Golgi apparatus. Mutation of one of these proteins called GMAP210 has recently been shown to cause a lethal skeletal disease in humans. The mechanisms by which occurs are poorly understood, as are the details of how GMAP210 and other tethering factors work in healthy cells. The aim of this proposal is to determine how GMAP210 function is regulated, focussing on its association with another protein of the Golgi apparatus that we have recently identified. This work will inform us of how the fundamental process of tethering takes place inside cells, and how defects in this process can lead to skeletal and possibly other types of disease in humans.

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。材料在这些隔室或细胞器之间运输在膜结合的小包中，称为囊泡。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。所有膜交通步骤都涉及一个称为束缚的过程，该过程是运输载体到其目的地隔室的初始附件。细胞中有许多束缚因子，包括高尔基体上的一个相关绑扎蛋白家族。这些称为GMAP210的蛋白质之一的突变最近已被证明会引起人类致命的骨骼疾病。发生的机制知之甚少，以及在健康细胞中GMAP210和其他束缚​​因子如何起作用的细节。该提案的目的是确定GMAP210功能如何受到调节，重点是与我们最近确定的高尔基体蛋白质的关联。这项工作将告知我们如何在细胞内部进行束缚的基本过程，以及该过程中的缺陷如何导致人类骨骼和可能其他类型的疾病。

项目成果

The golgin GMAP-210 is required for efficient membrane trafficking in the early secretory pathway.

• DOI: 10.1242/jcs.166710
• 发表时间: 2015-04-15
• 期刊: Journal of cell science
• 影响因子: 4
• 作者: Roboti P;Sato K;Lowe M
• 通讯作者: Lowe M

The cellular and physiological functions of the Lowe syndrome protein OCRL1.

• DOI: 10.1111/tra.12160
• 发表时间: 2014-05
• 期刊: Traffic (Copenhagen, Denmark)
• 作者: Mehta ZB;Pietka G;Lowe M
• 通讯作者: Lowe M

Coupling of vesicle tethering and Rab binding is required for in vivo functionality of the golgin GMAP-210.

• DOI: 10.1091/mbc.e14-10-1450
• 发表时间: 2015-02-01
• 期刊: Molecular biology of the cell
• 影响因子: 3.3
• 作者: Sato K;Roboti P;Mironov AA;Lowe M
• 通讯作者: Lowe M