Pacquelet Anne, Uhart Perrine, Tassan Jean-Pierre, Michaux Grégoire
Centre National de la Recherche Scientifique, UMR6290, Rennes, France Université de Rennes 1, Institut de Génétique et Développement de Rennes, 35043 Rennes, France
Centre National de la Recherche Scientifique, UMR6290, Rennes, France Université de Rennes 1, Institut de Génétique et Développement de Rennes, 35043 Rennes, France.
J Cell Biol. 2015 Sep 28;210(7):1085-99. doi: 10.1083/jcb.201503006.
During asymmetric cell division, the mitotic spindle and polarized myosin can both determine the position of the cytokinetic furrow. However, how cells coordinate signals from the spindle and myosin to ensure that cleavage occurs through the spindle midzone is unknown. Here, we identify a novel pathway that is essential to inhibit myosin and coordinate furrow and spindle positions during asymmetric division. In Caenorhabditis elegans one-cell embryos, myosin localizes at the anterior cortex whereas the mitotic spindle localizes toward the posterior. We find that PAR-4/LKB1 impinges on myosin via two pathways, an anillin-dependent pathway that also responds to the cullin CUL-5 and an anillin-independent pathway involving the kinase PIG-1/MELK. In the absence of both PIG-1/MELK and the anillin ANI-1, myosin accumulates at the anterior cortex and induces a strong displacement of the furrow toward the anterior, which can lead to DNA segregation defects. Regulation of asymmetrically localized myosin is thus critical to ensure that furrow and spindle midzone positions coincide throughout cytokinesis.
在不对称细胞分裂过程中，有丝分裂纺锤体和极化的肌球蛋白都能决定胞质分裂沟的位置。然而，细胞如何协调来自纺锤体和肌球蛋白的信号，以确保分裂通过纺锤体中区发生，目前尚不清楚。在这里，我们发现了一条新的途径，该途径对于在不对称分裂过程中抑制肌球蛋白并协调分裂沟和纺锤体的位置至关重要。在秀丽隐杆线虫的单细胞胚胎中，肌球蛋白定位于前皮质，而有丝分裂纺锤体则定位于后部。我们发现PAR-4/LKB1通过两条途径作用于肌球蛋白，一条是依赖膜收缩蛋白的途径，该途径也对泛素连接酶CUL-5有反应，另一条是不依赖膜收缩蛋白的途径，涉及激酶PIG-1/MELK。在缺乏PIG-1/MELK和膜收缩蛋白ANI-1的情况下，肌球蛋白在前皮质积累，并导致分裂沟强烈向前移位，这可能导致DNA分离缺陷。因此，对不对称定位的肌球蛋白的调节对于确保在整个胞质分裂过程中分裂沟和纺锤体中区的位置重合至关重要。
