Department of Microbiology and Cell Biology (MCB), Indian Institute of Science (IISc), Bangalore, India.
J Cell Biol. 2022 Dec 5;221(12). doi: 10.1083/jcb.202203127. Epub 2022 Oct 5.
In animal cells, spindle elongation during anaphase is temporally coupled with cleavage furrow formation. Spindle elongation during anaphase is regulated by NuMA/dynein/dynactin complexes that occupy the polar region of the cell membrane and are excluded from the equatorial membrane. How NuMA/dynein/dynactin are excluded from the equatorial membrane and the biological significance of this exclusion remains unknown. Here, we show that the centralspindlin (Cyk4/Mklp1) and its interacting partner RhoGEF Ect2 are required for NuMA/dynein/dynactin exclusion from the equatorial cell membrane. The Ect2-based (Ect2/Cyk4/Mklp1) and NuMA-based (NuMA/dynein/dynactin) complexes occupy mutually exclusive membrane surfaces during anaphase. The equatorial membrane enrichment of Ect2-based complexes is essential for NuMA/dynein/dynactin exclusion and proper spindle elongation. Conversely, NuMA-based complexes at the polar region of the cell membrane ensure spatially confined localization of Ect2-based complexes and thus RhoA. Overall, our work establishes that membrane compartmentalization of NuMA-based and Ect2-based complexes at the two distinct cell surfaces restricts dynein/dynactin and RhoA for coordinating spindle elongation with cleavage furrow formation.
在动物细胞中,有丝分裂后期的纺锤体伸长与胞质分裂沟的形成在时间上是偶联的。有丝分裂后期纺锤体的伸长受 NuMA/动力蛋白/动力蛋白激活蛋白复合物的调控,该复合物占据细胞膜的极区,而被排除在赤道膜之外。NuMA/动力蛋白/动力蛋白激活蛋白复合物是如何被排除在赤道膜之外的,以及这种排除的生物学意义尚不清楚。在这里,我们发现中心体纺锤体(Cyk4/Mklp1)及其相互作用的 RhoGEF Ect2 对于 NuMA/动力蛋白/动力蛋白激活蛋白复合物从赤道细胞膜中的排除是必需的。Ect2 为基础的(Ect2/Cyk4/Mklp1)和 NuMA 为基础的(NuMA/动力蛋白/动力蛋白激活蛋白)复合物在有丝分裂后期占据相互排斥的细胞膜表面。赤道膜上富集的 Ect2 为基础的复合物对于 NuMA/动力蛋白/动力蛋白激活蛋白复合物的排除和适当的纺锤体伸长是必需的。相反,细胞膜上的 NuMA 为基础的复合物确保了 Ect2 为基础的复合物在空间上局限于细胞膜的极区,从而保证了 RhoA 的定位。总的来说,我们的工作表明,NuMA 为基础的和 Ect2 为基础的复合物在两个不同的细胞膜表面的膜区室化限制了 dynein/动力蛋白激活蛋白复合物和 RhoA,以协调纺锤体伸长与胞质分裂沟的形成。