Deciphering pericentriolar material architecture and assembly principles using sub-diffraction imaging.

使用亚衍射成像解读中心粒周围材料结构和组装原理。

• 批准号: 355644-2013
• 负责人: Pelletier, Laurence
• 金额: $ 3.64万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=629466
• 关键词: Deciphering; pericentriolar; material; architecture; assembly

Centrosomes are composed of a pair of 9-fold symmetric barrel-shaped structures coined centrioles, which are surrounded by many proteins collectively referred to as pericentriolar material (PCM). PCM is responsible for several aspects of centrosome biogenesis and function including the nucleation and anchoring of microtubules. The mitotic spindle is an essential cellular structure that physically carries out the task of accurately transmitting chromosomes to progeny cells as they grow and divide. The two poles of the mitotic spindle are organized by centrosomes and without properly functioning centrosomes, the mitotic spindle will not form correctly. Therefore, in the absence of functional centrosomes, chromosomes would not segregate accurately to each daughter cell leading to a condition called aneuploidy that can cause devastating diseases like cancer. Traditionally described as amorphous, we have recently discovered using super-resolution microscopy that the PCM is much more ordered than generally thought. In particular, we found that different PCM proteins occupy distinct spatial domains in line with their functions in the regulation of centrosome biology. The major objective of this proposal is to build on this exciting new discovery and generate high-resolution spatial and temporal maps of the human centrosome. In addition, we will study the contribution of known centrosome proteins in the organization of centrosome domains and identify novel regulators of this process. Overall, this work will lead to a better mechanistic understanding of centrosome organization and assembly and how they are regulated during the cell cycle.

中心体由一对9重对称的筒状结构组成，称为中心粒，中心粒被许多蛋白质包围，统称为中心周围物质(PCM)。PCM负责中心体生物发生和功能的几个方面，包括微管的成核和锚定。有丝分裂纺锤体是一种基本的细胞结构，在子代细胞生长和分裂过程中，它在物理上执行准确向子代细胞传递染色体的任务。有丝分裂纺锤体的两极是由中心体组织的，如果中心体功能不正常，有丝分裂纺锤体就不会正确形成。因此，在没有功能中心体的情况下，染色体不会准确地分离到每个子细胞，从而导致一种称为非整倍体的情况，这种情况可能会导致癌症等毁灭性的疾病。传统上被描述为无定形的，我们最近使用超分辨率显微镜发现，PCM比通常认为的更有序。特别是，我们发现不同的PCM蛋白根据它们在中心体生物学调节中的功能占据了不同的空间域。这项提议的主要目标是在这一令人兴奋的新发现的基础上，生成人类中心体的高分辨率空间和时间地图。此外，我们还将研究已知的中心体蛋白在中心体结构域组织中的作用，并确定这一过程的新调节因子。总体而言，这项工作将导致对中心体组织和组装以及它们在细胞周期中如何调控的更好的机械性理解。