Division of Molecular Biology, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia.
Department of Physics, Faculty of Science, University of Zagreb, Bijenička cesta 32, 10000 Zagreb, Croatia.
Cell Rep. 2022 Aug 2;40(5):111169. doi: 10.1016/j.celrep.2022.111169.
Chromosome alignment at the spindle equator promotes proper chromosome segregation and depends on pulling forces exerted at kinetochore fiber tips together with polar ejection forces. However, kinetochore fibers are also subjected to forces driving their poleward flux. Here we introduce a flux-driven centering model that relies on flux generated by forces within the overlaps of bridging and kinetochore fibers. This centering mechanism works so that the longer kinetochore fiber fluxes faster than the shorter one, moving the kinetochores toward the center. We develop speckle microscopy in human spindles and confirm the key prediction that kinetochore fiber flux is length dependent. Kinetochores are better centered when overlaps are shorter and the kinetochore fiber flux slower than the bridging fiber flux. We identify Kif18A and Kif4A as overlap and flux regulators and NuMA as a fiber coupler. Thus, length-dependent sliding forces exerted by the bridging fiber onto kinetochore fibers support chromosome alignment.
染色体在纺锤体赤道处的排列促进了正确的染色体分离，这依赖于着丝粒纤维末端的拉力以及极向推出力。然而，着丝粒纤维也受到驱使它们向极部流动的力的作用。在这里，我们引入了一个流动驱动的中心定位模型，该模型依赖于桥连和着丝粒纤维重叠处的力产生的流动。这个中心定位机制的工作原理是，较长的着丝粒纤维比较短的纤维流动更快，从而将着丝粒移动到中心。我们在人类纺锤体中开发了斑点显微镜，并证实了关键预测，即着丝粒纤维流动与长度有关。当重叠较短且着丝粒纤维流动比桥连纤维流动慢时，着丝粒的中心位置更好。我们确定 Kif18A 和 Kif4A 是重叠和流动的调节剂，NuMA 是纤维连接器。因此，桥连纤维施加在着丝粒纤维上的长度依赖性滑动力支持染色体的排列。
