Regulation of dictyostelium type 1 myosins

1 型网柄菌肌球蛋白的调节

• 批准号: 391522-2011
• 负责人: Cote, Graham
• 金额: $ 2.62万
• 依托单位: Queen's University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=573047
• 关键词: Regulation; dictyostelium; type; myosins

Movement is one of the fundamental properties of living cells. We are studying an amoeba, Dictyostelium discoideum, that serves as an excellent model system for investigating the molecular mechanisms that underlie cell motility. Dictyostelium amoeba crawl over surfaces, extend and retract protrusions, change shape, engulf other microorganisms and divide by splitting into two. All of these types of movement depend on the interaction of a myosin motor protein with a network of filaments made up of the protein actin. Myosins have the unique ability to convert chemical energy into movement along actin filaments. Most cells contain several different types of myosin, all of which consist of a large subunit, or heavy chain, that is bound to one or more smaller subunits, or more light chains. The light chains play a critical role in regulating the activity of myosin, but surprisingly, for most myosins the identity of the light chain subunits remain unknown. Over the last several years we have made considerable progress in identifying the light chain subunits of the Dictyostelium myosins. Unexpectedly, we have discovered that most Dictyostelium myosins have unique light chains. We have also discovered another mechanism that regulates myosin, which involves a protein kinase, termed PakB, that can attach a phosphate to the heavy chain of the myosin. In the proposed research we will examine how the myosin heavy chains and light chains recognize each other and how the choice of the light chain effects the function of myosin in the cell. We also will carry out studies to better understand the regulation of PakB. Together, these studies will provide important new insights into the regulation of myosin motor proteins in cells. Over the last five years three MSc students and three PhD students have been trained on this project. New students trained on this project will gain experience in a range of techniques, including molecular biology, protein biochemistry, structural analysis and cell biology, that are in demand by academic researchers and by biotechnology and pharmaceutical industries.

运动是活细胞的基本特性之一。 我们正在研究一种变形虫，盘基网柄菌，它是研究细胞运动分子机制的优秀模型系统。 盘基网柄菌阿米巴在表面爬行，伸展和缩回突出物，改变形状，吞噬其他微生物并分裂成两部分。所有这些类型的运动都取决于肌球蛋白运动蛋白与由肌动蛋白组成的细丝网络的相互作用。 肌球蛋白具有将化学能转化为沿着肌动蛋白丝运动的独特能力。 大多数细胞含有几种不同类型的肌球蛋白，所有肌球蛋白均由一个大亚基或重链组成，与一个或多个较小亚基或多条轻链结合。 轻链在调节肌球蛋白的活性中发挥着关键作用，但令人惊讶的是，对于大多数肌球蛋白来说，轻链亚基的身份仍然未知。 在过去的几年中，我们在鉴定盘基网柄菌肌球蛋白的轻链亚基方面取得了相当大的进展。 出乎意料的是，我们发现大多数盘基网柄菌肌球蛋白都具有独特的轻链。 我们还发现了另一种调节肌球蛋白的机制，其中涉及一种名为 PakB 的蛋白激酶，它可以将磷酸盐附着到肌球蛋白的重链上。 在拟议的研究中，我们将研究肌球蛋白重链和轻链如何相互识别以及轻链的选择如何影响细胞中肌球蛋白的功能。 我们还将开展研究以更好地了解 PakB 的调控。 总之，这些研究将为细胞中肌球蛋白运动蛋白的调节提供重要的新见解。 在过去的五年里，三名硕士生和三名博士生接受了该项目的培训。 接受该项目培训的新生将获得学术研究人员以及生物技术和制药行业所需的一系列技术经验，包括分子生物学、蛋白质生物化学、结构分析和细胞生物学。