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都由不同的区室组成，每个区室都有独特的组成和特定的功能。物质在称为囊泡的膜结合包中在这些区室或细胞器之间运输。这个过程被称为膜运输，是细胞和生物体整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与细胞表面融合的囊泡中的细胞中释放出来，而生长因子和死亡细胞则从细胞表面吸收的囊泡中从血流中清除。细胞中的主要隔室之一是高尔基体，它是一组称为池的扁平膜袋的集合，这些膜袋彼此层叠形成堆叠。高尔基体有两个主要功能：它负责修饰蛋白质和脂质上存在的糖链；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内的其他区室。蛋白质的正确修饰和递送至关重要。高尔基体功能和膜运输的缺陷是导致许多人类疾病的原因。此外，膜交通机械的组件，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/或逃避免疫系统的检测。因此，了解高尔基体如何在分子水平上发挥作用非常重要。所有膜运输步骤都涉及一个称为“系链”的过程，这是运输载体与其目的地隔室的初始连接。细胞中有许多束缚因子，包括高尔基体上的一系列相关束缚蛋白。其中一种名为 GMAP210 的蛋白质的突变最近被证明会导致人类致命的骨骼疾病。人们对这种现象的发生机制知之甚少，GMAP210 和其他束缚​​因子如何在健康细胞中发挥作用的细节也是如此。该提案的目的是确定 GMAP210 功能是如何调节的，重点关注它与我们最近发现的另一种高尔基体蛋白质的关联。这项工作将告诉我们细胞内束缚的基本过程是如何发生的，以及这个过程中的缺陷如何导致人类骨骼疾病和可能的其他类型的疾病。

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

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

GOLGIN GMAP-210的体内功能需要囊泡绑定和RAB结合的耦合。

• 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

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