Function of leucine-rich repeat kinase 2 (LRRK2) in endosomal trafficking

富含亮氨酸重复激酶 2 (LRRK2) 在内体运输中的功能

• 批准号: RGPIN-2017-06062
• 负责人: Mcpherson, Peter
• 金额: $ 3.64万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=689947
• 关键词: Function; leucine; rich; repeat; kinase

The cell surface is defined by the plasma membrane, which separates the cell interior from the external world. The plasma membrane is studded with proteins that have multiple functions, for example allowing a cell to interact with other cells or to interact with essential cellular nutrients. These proteins are continuously brought into the cell in a process called endocytosis. Following internalization the proteins are delivered to a membrane compartment called endosomes that are a hub for protein sorting. From endosomes the proteins are either targeted for degradation as part of protein renewal or are recycled back to the plasma membrane for continued function. Through these activities endosomes control the levels and localization of a myriad of proteins and thus cell function. This project will examine the function of two specific proteins and how they interact to control key aspects of this fundamental cellular process. There are a large group of scientists, both in Canada and throughout the world that study how proteins are sorted in endosomes. Our work will enhance this field but perhaps more importantly, alterations in these pathways contribute to diseases that are of great concern to Canadians including neurodegenerative diseases and cancer. Our work will lay the foundation for further studies on these important topics.

细胞表面由质膜定义，它将细胞内部与外部世界分开。质膜上布满了具有多种功能的蛋白质，例如允许细胞与其他细胞相互作用或与必需的细胞营养物质相互作用。这些蛋白质通过称为内吞作用的过程不断进入细胞。内化后，蛋白质被输送到称为内体的膜室，内体是蛋白质分选的中心。来自内体的蛋白质要么作为蛋白质更新的一部分被靶向降解，要么被回收回质膜以继续发挥功能。通过这些活动，内体控制多种蛋白质的水平和定位，从而控制细胞功能。该项目将研究两种特定蛋白质的功能以及它们如何相互作用以控制这一基本细胞过程的关键方面。加拿大和世界各地都有一大批科学家研究蛋白质如何在内体中分类。我们的工作将加强这一领域，但也许更重要的是，这些途径的改变会导致加拿大人非常关心的疾病，包括神经退行性疾病和癌症。我们的工作将为这些重要主题的进一步研究奠定基础。