Vaudano Alexandre Pierre, Schwager Françoise, Gotta Monica, Barbieri Sofia
Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland.
Proc Natl Acad Sci U S A. 2024 Dec 24;121(52):e2407517121. doi: 10.1073/pnas.2407517121. Epub 2024 Dec 17.
Proteins become asymmetrically distributed in the one-cell embryo thanks to reaction-diffusion mechanisms that are often entangled in complex feedback loops. Cortical polarity drives the enrichment of the RNA-binding proteins MEX-5 and MEX-6 in the anterior cytoplasm through concentration gradients. MEX-5 and MEX-6 promote the patterning of other cytoplasmic factors, including that of the anteriorly enriched mitotic polo-like kinase PLK-1, but also contribute to proper cortical polarity. The gradient of MEX-5 forms through a differential-diffusion mechanism. How MEX-6 establishes a gradient and how MEX-5 and MEX-6 regulate cortical polarity is not known. Here, we reveal that the two MEX proteins develop concentration asymmetries via similar mechanisms, but despite their strong sequence homology, they differ in terms of how their concentration gradients are regulated. We find that PLK-1 promotes the enrichment of MEX-5 and MEX-6 at the anterior through different circuits: PLK-1 influences the MEX-5 gradient indirectly by regulating cortical polarity while it modulates the formation of the gradient of MEX-6 through its physical interaction with the protein. We thus propose a model in which PLK-1 mediates protein circuitries between MEX-5, MEX-6, and cortical proteins to faithfully establish and maintain polarity.
由于反应扩散机制，蛋白质在单细胞胚胎中呈不对称分布，而这些机制常常纠缠于复杂的反馈回路中。皮质极性通过浓度梯度驱动RNA结合蛋白MEX-5和MEX-6在前部细胞质中富集。MEX-5和MEX-6促进其他细胞质因子的模式形成，包括前部富集的有丝分裂极样激酶PLK-1的模式形成，但也有助于维持适当的皮质极性。MEX-5的梯度通过差异扩散机制形成。MEX-6如何建立梯度以及MEX-5和MEX-6如何调节皮质极性尚不清楚。在这里，我们揭示这两种MEX蛋白通过类似机制产生浓度不对称，但尽管它们具有很强的序列同源性，它们在浓度梯度的调节方式上存在差异。我们发现PLK-1通过不同途径促进MEX-5和MEX-6在前部的富集：PLK-1通过调节皮质极性间接影响MEX-5梯度，而它通过与该蛋白的物理相互作用调节MEX-6梯度的形成。因此，我们提出了一个模型，其中PLK-1介导MEX-5、MEX-6和皮质蛋白之间的蛋白质回路，以忠实地建立和维持极性。
