发表机构
Center for Computational Biology, Flatiron Institute; Department of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University; Courant Institute, New York University（计算生物学中心，Flatiron研究所; 细胞与发育生物学系，范伯格医学院，西北大学; 库朗数学科学研究所，纽约大学）
机构由 AI 辅助整理，请以论文原文为准。AI 中文总结
本研究结合多类实验与建模，揭示果蝇卵母细胞通过位置依赖的皮质交换耦合细胞质扩散，将细胞骨架不对称转化为oskar mRNA的稳定后部定位，明确了关键调控参数。
AI 中文摘要
果蝇卵母细胞的前后极化需要oskar mRNA定位于后部。oskar mRNA由位于前部的滋养细胞产生，被转运至卵母细胞内，并组装成oskar-Staufen核糖核蛋白颗粒（RNPs）。这些RNPs随后在卵母细胞内移动并与皮质相互作用，其中肌球蛋白-V（myosin-V）将它们结合到肌动蛋白网络上，驱动蛋白-1（kinesin-1）则沿着锚定在皮质上的微管将它们移除。这种皮质层面的“拔河”过程发生在微管密度从前部到后部逐渐降低的背景下。目前尚不清楚细胞质运输与皮质结合、解离之间的相互作用如何形成稳定的后部帽状结构。本研究结合定量显微镜、光转换实验、实验扰动及生物物理建模，证明后部定位源于位置依赖的皮质交换与细胞质扩散的耦合。我们的模型考虑了RNPs的相分离倾向，表明决定观察到的定位模式的两个关键参数是oskar的总量以及皮质解离速率与结合速率的比值（即交换平衡常数）。在野生型oskar体积分数下，测得的交换常数可使oskar在不发生相分离的情况下定位于后部皮质；若平衡被打破，例如通过提高解离速率，oskar会不可逆地相分离为细胞质液滴，这与我们实验扰动的观察结果一致。本研究结果揭示了在oskar RNPs自吸引的作用下，体扩散与皮质交换如何将细胞骨架不对称性转化为稳定的发育极性。
英文摘要
Anterior-posterior polarization in the Drosophila oocyte requires posterior localization of oskar mRNA. oskar mRNA is produced in the anteriorly situated nurse cells, moved into the oocyte, and assembled into oskar-Staufen ribonucleoprotein particles (RNPs). These RNPs then move through the oocyte and interact with the cortex, where myosin-V binds them to the actin network and kinesin-1 removes them along cortically anchored microtubules. This cortical tug-of-war takes place against an anterior-to-posterior decrease in microtubule density. How the interplay between cytoplasmic transport and cortical binding and unbinding produces a stable posterior cap is unclear. Here, we combine quantitative microscopy, photoconversion experiments, experimental perturbations, and biophysical modeling to show that posterior localization emerges from position-dependent cortical exchange coupled to cytoplasmic diffusion. Our model, which accounts for the tendency of RNPs to demix, suggests that two key parameters that determine the observed localization pattern are the total amount of oskar and the ratio of cortical unbinding to binding rates (the exchange equilibrium constant). Given oskar volume fractions in wild-type, the measured exchange constant is such that oskar localizes to the posterior cortex without demixing. If the balance is broken, say by increasing unbinding rates, oskar irreversibly demixes into cytoplasmic droplets. This is consistent with observations from our experimental perturbations. Our results show how bulk diffusion and cortical exchange, in the face of oskar RNPs' self-attraction, convert a cytoskeletal asymmetry into robust developmental polarity.
