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: 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=572628
• 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 重对称的桶状结构（称为中心粒）组成，中心粒周围有许多蛋白质，统称为中心粒周围材料（PCM）。 PCM 负责中心体生物发生和功能的多个方面，包括微管的成核和锚定。有丝分裂纺锤体是一种重要的细胞结构，在子代细胞生长和分裂时，它在物理上执行将染色体准确传递给子代细胞的任务。有丝分裂纺锤体的两极由中心体组织，如果没有正常发挥功能的中心体，有丝分裂纺锤体将无法正确形成。因此，在缺乏功能性中心体的情况下，染色体将无法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，这种情况可能导致癌症等毁灭性疾病。传统上将相变材料描述为非晶态，但我们最近使用超分辨率显微镜发现相变材料比通常认为的更加有序。特别是，我们发现不同的 PCM 蛋白占据不同的空间域，与其在中心体生物学调节中的功能一致。该提案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图。此外，我们将研究已知中心体蛋白在中心体结构域组织中的贡献，并确定该过程的新调节因子。 总的来说，这项工作将有助于更好地理解中心体的组织和组装以及它们在细胞周期中的调节方式。