Department of Cell Biology and Human Anatomy, University of California, Davis, School of Medicine, Davis, CA 95616, USA.
Department of Biomedical Engineering, University of California, Davis, Davis, CA 95616, USA.
J Cell Sci. 2021 Jul 15;134(14). doi: 10.1242/jcs.258897. Epub 2021 Jul 26.
At the onset of mitosis, centrosomes expand the pericentriolar material (PCM) to maximize their microtubule-organizing activity. This step, termed centrosome maturation, ensures proper spindle organization and faithful chromosome segregation. However, as the centrosome expands, how PCM proteins are recruited and held together without membrane enclosure remains elusive. We found that endogenously expressed pericentrin (PCNT), a conserved PCM scaffold protein, condenses into dynamic granules during late G2/early mitosis before incorporating into mitotic centrosomes. Furthermore, the N-terminal portion of PCNT, enriched with conserved coiled-coils (CCs) and low-complexity regions (LCRs), phase separates into dynamic condensates that selectively recruit PCM proteins and nucleate microtubules in cells. We propose that CCs and LCRs, two prevalent sequence features in the centrosomal proteome, are preserved under evolutionary pressure in part to mediate liquid-liquid phase separation, a process that bestows upon the centrosome distinct properties critical for its assembly and functions.
在有丝分裂开始时，中心体扩展中心粒周围物质（PCM）以最大限度地提高其微管组织活性。这一步骤称为中心体成熟，可确保正确的纺锤体组织和忠实的染色体分离。然而，随着中心体的扩大，PCM 蛋白如何在没有膜封闭的情况下被招募并保持在一起仍然难以捉摸。我们发现，内源性表达的中心粒周围蛋白（PCNT）是一种保守的 PCM 支架蛋白，在进入有丝分裂中心体之前，在晚期 G2/早期有丝分裂过程中凝聚成动态颗粒。此外，富含保守卷曲螺旋（CC）和低复杂度区域（LCR）的 PCNT N 端部分在细胞中相分离成动态凝聚物，这些凝聚物选择性地招募 PCM 蛋白并起始微管的形成。我们提出，CC 和 LCR 是中心体蛋白质组中两种常见的序列特征，它们在进化压力下得以保留，部分原因是介导液-液相分离，这一过程赋予中心体独特的特性，对其组装和功能至关重要。
