Actin synchronizes chromosome capture by microtubules in starfish oocyte meiosis

Chromosome capture by microtubules is an early step of cell division essential for alignment and subsequent separation of sister chromatids. Failure to transmit even one chromosome results in aneuploidy, a common cause of infertility, genetic disorders or cancer. The canonical mechanism of ‘search and capture’ by dynamic astral microtubules has been validated by recent studies, and additionally revealed mechanisms that facilitate microtubule search, ensuring rapid and efficient capture of chromosomes in somatic cells. However, in specialized cell types such as oocytes with large nucleus chromosomes are located much further from microtubule asters. In these cells, the models that work in small somatic cells are insufficient to explain chromosome capture. Recently, the Lénárt group has shown that in starfish oocytes an actin-driven mechanism facilitates chromosome congression and is required to prevent chromosome loss: a contractile actin meshwork transports chromosomes to within the capture range of microtubule asters of approximately 30 µm. How these actin- and microtubule-driven mechanisms of chromosome capture are coordinated remained an open question. Here, I investigated the cooperation between the actin meshwork transporting chromosomes and capture by microtubules in meiosis of starfish oocytes using high spatio-temporal resolution tracking of chromosome motion in 3D combined with drug-perturbation experiments. This assay allowed me to characterize chromosome capture kinetics during the two-staged chromosome congression under different conditions. I find that the actin meshwork, while transporting the distal chromosomes to the vicinity of microtubule asters, also synchronizes their capture. I show that this synchronizing effect is due to an actin-dependent block of chromosome capture active for approx. 5 minutes after NEBD. As a result, chromosomes close to microtubule asters – that in principle could be captured immediately after NEBD – are captured simultaneously with chromosomes transported from distal nuclear locations by the actin meshwork at approx. 5-15 minutes after NEBD and independent of their distance from the asters. I show that this delay in the capture of the proximally located chromosomes cannot be explained by altered microtubule dynamics when growing through the actin meshwork. The delay is also not the consequence of physical entrapment in the actin network ‘holding back’ chromosomes, because capture is not delayed in slowed or even fully stabilized actin networks. Together, my results point to an actin-dependent mechanism, which prevents the formation of lateral kinetochore-microtubule attachments. Synchronous disassembly of these F-actin structures exposes kinetochores and thereby synchronizes chromosome capture. This is a first description of a mechanism by which the actin cytoskeleton directly affects spindle assembly, and which actively controls and coordinates chromosome search and capture. I show how this mechanism coordinates chromosome congression in the specialized oocyte nucleus, but it is interesting to speculate whether such mechanisms may have a broader relevance for example to synchronize mitotic events such as cell rounding mediated by the actin cytoskeleton with spindle assembly. The detailed molecular mechanism of how F-actin prevents chromosome-microtubule attachment remains an exciting open question for the future studies