Temasek Life-sciences Laboratory, 1 Research Link, National University of Singapore, Singapore 117604, Singapore.
Mechanobiology Institute, National University of Singapore, T-Lab, 5A Engineering Drive 1, Singapore 117411, Singapore.
Nat Cell Biol. 2017 Aug;19(8):988-995. doi: 10.1038/ncb3577. Epub 2017 Jul 24.
Cell polarization enables zygotes to acquire spatial asymmetry, which in turn patterns cellular and tissue axes during development. Local modification in the actomyosin cytoskeleton mediates spatial segregation of partitioning-defective (PAR) proteins at the cortex, but how mechanical changes in the cytoskeleton are transmitted to PAR proteins remains elusive. Here we uncover a role of actomyosin contractility in the remodelling of PAR proteins through cortical clustering. During embryonic polarization in Caenorhabditis elegans, actomyosin contractility and the resultant cortical tension stimulate clustering of PAR-3 at the cortex. Clustering of atypical protein kinase C (aPKC) is supported by PAR-3 clusters and is antagonized by activation of CDC-42. Cortical clustering is associated with retardation of PAR protein exchange at the cortex and with effective entrainment of advective cortical flows. Our findings delineate how cytoskeleton contractility couples the cortical clustering and long-range displacement of PAR proteins during polarization. The principles described here would apply to other pattern formation processes that rely on local modification of cortical actomyosin and PAR proteins.
细胞极化使受精卵获得空间不对称性，进而在发育过程中形成细胞和组织轴。肌动球蛋白细胞骨架的局部修饰介导了有丝分裂缺陷（PAR）蛋白在皮层的空间分离，但细胞骨架中的机械变化如何传递到 PAR 蛋白仍然难以捉摸。在这里，我们揭示了肌动球蛋白收缩在通过皮层聚类重塑 PAR 蛋白中的作用。在秀丽隐杆线虫胚胎极化过程中，肌动球蛋白收缩和由此产生的皮层张力刺激 PAR-3 在皮层的聚集。非典型蛋白激酶 C（aPKC）的聚集得到 PAR-3 簇的支持，并被 CDC-42 的激活所拮抗。皮层聚类与 PAR 蛋白在皮层交换的延迟以及有效的平流皮层流的牵引有关。我们的发现描绘了细胞骨架收缩如何在极化过程中偶联 PAR 蛋白的皮层聚类和长程位移。这里描述的原则适用于其他依赖于皮层肌动球蛋白和 PAR 蛋白局部修饰的模式形成过程。
