Asymmetric cell division-specific phosphorylation of PAR-3 regulates neuroblasts polarisation and sensory organ formation in Drosophila
Asymmetric cell division-specific phosphorylation of PAR-3 regulates neuroblasts polarisation and sensory organ formation in Drosophila
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DOI：
10.1101/2023.07.26.550680
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发表时间：
2023-07
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影响因子：
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通讯作者：
Nicolas Loyer;Elizabeth K J Hogg;Hayley Shaw;D. Murray;Greg M. Findlay;J. Januschke
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作者：
Nicolas Loyer;Elizabeth K J Hogg;Hayley Shaw;D. Murray;Greg M. Findlay;J. Januschke
发育过程中不同细胞命运的产生取决于祖细胞的不对称细胞分裂。在果蝇的中枢和外周神经系统中，分别称为神经母细胞或感觉器官前体的祖细胞在有丝分裂期间使用PAR极性来控制其子细胞中的细胞命运决定。极性和细胞周期如何耦合，以及细胞周期机制如何调节PAR蛋白功能和细胞命运决定知之甚少。在这里，我们产生了一个类似物敏感的等位基因CDK 1和揭示，其部分抑制减弱，但不废除顶端极性在胚胎和幼虫神经母细胞，并导致缺陷的极化命运决定因素。我们描述了一种新的体内磷酸化的巴祖卡，果蝇同源的PAR-3，丝氨酸180，一个共识CDK磷酸化位点。值得注意的是，丝氨酸180的磷酸化发生在不对称分裂的神经母细胞和感觉器官前体细胞中，而不是在它们对称分裂的邻居中。我们进一步表明，丝氨酸180磷酸突变体破坏了神经母细胞和感觉器官前体的感觉器官形成的基础极化的时间。最后，我们表明，CDK 1可以在体外磷酸化人PARD 3，提示CDK 1和PAR-3之间的保守激酶-底物关系。
The generation of distinct cell fates during development depends on asymmetric cell division of progenitor cells. In the central and peripheral nervous system of Drosophila, progenitor cells respectively called neuroblasts or sensory organ precursors use PAR polarity during mitosis to control cell fate determination in their daughter cells. How polarity and the cell cycle are coupled, and how the cell cycle machinery regulates PAR protein function and cell fate determination is poorly understood. Here, we generate an analog sensitive allele of CDK1 and reveal that its partial inhibition weakens but does not abolish apical polarity in embryonic and larval neuroblasts, and leads to defects in polarisation of fate determinants. We describe a novel in vivo phosphorylation of Bazooka, the Drosophila homolog of PAR-3, on Serine180, a consensus CDK phosphorylation site. Remarkably, phosphorylation of Serine180 occurs in asymmetrically dividing neuroblasts and sensory organ precursors, and not in their symmetrically dividing neighbours. We further show that Serine180 phosphomutants disrupt the timing of basal polarisation in neuroblasts and sensory organ formation in sensory organ precursors. Finally, we show that CDK1 can phosphorylate human PARD3 in vitro, suggestive of a conserved kinase-substrate relationship between CDK1 and PAR-3.