Garcia Jason Q, Mouilleau Vincent, Ng Henry, Zhao Xiang, Morgan David O, Guo Su
Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94143, USA.
Tetrad Graduate Program, University of California, San Francisco, San Francisco, CA 94143, USA.
Sci Adv. 2025 May 16;11(20):eadq3858. doi: 10.1126/sciadv.adq3858. Epub 2025 May 14.
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 Ser of zebrafish Par-3 is phosphorylated by Aurora kinase A (AurkA) in vitro. Expression of the nonphosphorylated mutant Par-3 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.
在放射状胶质细胞前体（RGP）进行不对称细胞分裂（ACD）期间，皮质极性调节因子Par-3在细胞质中被检测到，与动力蛋白和Notch配体DeltaD（Dld）共定位。是什么将Par-3驱动到细胞质中及其对RGP ACD的影响仍然未知。在这里，我们使用体内延时成像观察细胞质中的Par-3，发现在体外斑马鱼Par-3的丝氨酸被极光激酶A（AurkA）磷酸化。非磷酸化突变体Par-3的表达对胚胎发育产生显性负性影响，减少细胞质中的Par-3，并破坏皮质Par-3和Dld内体的前后不对称性，进而影响子细胞命运。有丝分裂RGP中的AurkA显示出动态的中心体周围分布，优先在细胞后侧与皮质Par-3短暂共定位。AurkA对于增加细胞质中的Par-3同时减少皮质中的Par-3、破坏Par-3的皮质不对称性以及扰乱极化的Dld内体动力学来说既是必需的也是充分的。这些发现表明，AurkA调节对于ACD和子细胞命运至关重要的Par-3皮质-细胞质动力学。
