The Regulation Of Cytoplasmic F-actin Structure On Mitotic Spindle Plasticity

Parental cells need to transmit their genetic materials to daughter cells with high-fidelity in mitosis. To accomplish this, they need a special machine which can accurately segregates the chromosomes during mitosis. We call it mitotic spindle. Anything that is abnormal happening to spindle, no matter in orientation or in shape, can cause great damage to cells. The direct consequence is that cells can’t complete its mission. So, searching for the factors that contribute to the regulation of spindle can be of great significance.The orientation and position of spindle are called the dynamic geometry characteristics of the spindle, which is essential for the cell fate. Proper spindle positioning and orientation are essential for accurate mitosis and require microtubule-actin filament (F-actin) interactions. Traditional research mostly focused on the cell cortex actins and the interactions between the astral microtubule and the cell cortex, including some proteins such as NuMA, Dynein and so on. Although mounting evidence demonstrates the role of F-actin in cell cortex, it has remained elusive as to structure and function of cytoplasmic F-actin based networks in spindle geometry. Most of recent research is limited to mitosis and meiosis in large oocyte, egg or early embryo cells, and most of these experiments are conducted in relatively primary cells and fission yeast. Here we show a novel F-actin ring-like structure surrounding the mitotic spindle which is essential for accurate mitosis. The F-actin network, comprising myosin, MISP and other actin-binding proteins, is required to generate the sustained oscillation and plasticity for the mitotic spindle. Through a series of small molecule inhibitors, we found that proverbial kinases Plkl Mpsl and another protein Myosin may participate in the regulation of this structure. What’s more, we found that this structure influences the dynamics of spindle and finally equal-size cell division. Surprisingly, MISP is a newly-found F-actin-binding protein. Suppression of MISP by siRNA-mediated knockdown perturbs spindle plasticity, which results in an aberrant spindle position and asymmetric division.Thus, we found a novel mitotic function of cytoplasmic actin network, which open up a new direction for the research on actin.