Phosphorylation by Aurora kinase A facilitates cortical-cytoplasmic dynamics of Par-3 in asymmetric division of radial glia progenitors

IF 11.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Advances Pub Date : 2025-05-14 DOI:10.1126/sciadv.adq3858

Jason Q. Garcia, Vincent Mouilleau, Henry Ng, Xiang Zhao, David O. Morgan, Su Guo

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Abstract

During asymmetric cell division (ACD) of radial glia progenitors (RGPs), the cortical polarity regulator Par-3 is detected in the cytoplasm colocalizing with dynein and Notch ligand DeltaD (Dld). What drives Par-3 to the cytoplasm and its impact on RGP ACD remain unknown. Here, we visualize cytoplasmic Par-3 using in vivo time-lapse imaging and find that Ser⁹⁵⁴ of zebrafish Par-3 is phosphorylated by Aurora kinase A (AurkA) in vitro. Expression of the nonphosphorylated mutant Par-3^S954A dominant negatively affects embryonic development, reduces cytoplasmic Par-3, and disrupts the anteroposterior asymmetry of cortical Par-3 and Dld endosomes and, in turn, daughter cell fate. AurkA in mitotic RGPs shows dynamic pericentrosomal distribution that transiently colocalizes with cortical Par-3 preferentially on the posterior side. AurkA is both necessary and sufficient to increase cytoplasmic while decreasing cortical Par-3, disrupts Par-3 cortical asymmetry, and perturbs polarized Dld endosome dynamics. These findings suggest that AurkA regulates Par-3 cortical-cytoplasmic dynamics that is critical for ACD and daughter cell fate.

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极光激酶A的磷酸化促进了Par-3在放射状胶质祖细胞不对称分裂中的皮质-细胞质动力学

在放射状胶质祖细胞（RGPs）的非对称细胞分裂（ACD）过程中，在与动力蛋白和缺口配体δ tad （Dld）共定位的细胞质中检测到皮质极性调节因子Par-3。是什么驱使Par-3进入细胞质及其对RGP ACD的影响尚不清楚。在这里，我们使用体内延时成像技术可视化了斑马鱼的细胞质Par-3，发现Par-3的Ser954在体外被极光激酶A （AurkA）磷酸化。非磷酸化突变体Par-3S954A显性表达对胚胎发育产生负面影响，减少细胞质Par-3，破坏皮质Par-3和Dld内体的前后不对称，进而影响子细胞的命运。有丝分裂RGPs中的AurkA表现为动态的核内体周围分布，并短暂地与皮质Par-3优先在后侧共定位。AurkA是增加细胞质而降低皮质Par-3的必要和充分条件，破坏皮质Par-3的不对称性，扰乱极化Dld内体动力学。这些发现表明，AurkA调节Par-3皮质细胞质动力学，这对ACD和子细胞的命运至关重要。

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来源期刊

Science Advances 综合性期刊-综合性期刊

CiteScore

21.40

自引率

1.50%

发文量

1937

审稿时长

29 weeks

期刊介绍： Science Advances, an open-access journal by AAAS, publishes impactful research in diverse scientific areas. It aims for fair, fast, and expert peer review, providing freely accessible research to readers. Led by distinguished scientists, the journal supports AAAS's mission by extending Science magazine's capacity to identify and promote significant advances. Evolving digital publishing technologies play a crucial role in advancing AAAS's global mission for science communication and benefitting humankind.