Dynein: a mighty coordinator of cell division
EPFL scientists have discovered how the molecular motor protein dynein regulates the all-important separation of centrosomes during cell division.
When cell division begins, the two centrosomes must separate in a timely and accurate fashion to ensure the proper assembly of the bipolar mitotic spindle, which is essential for the faithful segregation of the genetic material to daughter cells. One of the main actors of centrosome separation is dynein, a motor protein best known for its ability to transport cargo by “walking” along microtubules and to exert forces on them. However, how dynein coordinates centrosome separation over time and space has been elusive.
In a study recently published in Cell Reports, Pierre Gönczy’s group at EPFL uncovered how dynein proteins on two different locations in the cell work together to ensure robust separation of centrosomes. The dynein in this case are located on the surface of the nucleus and at the cell cortex, which is a contractile actomyosin meshwork beneath the cell membrane. The group combined 3D live microscopy and computational modeling to analyze this process in the first cell division of the C. elegans embryo, which is well suited for dissecting cell mechanics.
Because dynein is found in different locations in the cell, it had not been clear previously where or how it influences centrosome separation. In the study, led by PhD student Alessandro De Simone, the researchers selectively removed dynein from the nuclear surface or the cell cortex to determine how these two protein pools work together to power centrosome separation.
The scientists found that nuclear dynein pulls centrosomes towards the nucleus and ensures that their separation is properly regulated in time and space. At the same time, dynein in the cell cortex acts as a coupling device that transmits forces produced by a flow of the actomyosin cortex, which the centrosomes themselves triggered earlier in the cell cycle.
The study demonstrates for the first time how the initial events of cell polarization, which occur shortly after fertilization, are coordinated with centrosome separation. The authors propose that the mechanisms unearthed in C. elegans could be broadly utilized in other organisms, including humans, to promote correct bipolar spindle assembly and thus ensure faithful segregation of the genetic material.
Figure: The represented embryo (grey shadow) is constituted of a single ellipsoidal cell that has been just fertilized. The sperm and oocyte DNA form two separate pronuclei (blue and dark green spheres respectively), positioned at opposite sides of the embryo. Centrosomes (small light green spheres) are attached to the sperm pronucleus and nucleate microtubule fibers (white lines). Dynein motors either at the surface of the pronuclei (blue points) or at the cell cortex (red points at embryo boundary) bind to microtubules, exert force on them, and thus separate centrosomes.
This work was supported by the Swiss National Science Foundation.
De Simone A, Nédélec F, Gönczy P. Dynein Transmits Polarized Actomyosin Cortical Flows to Promote Centrosome Separation.Cell Reports 14:1–13, 08 March 2016. DOI: 10.1016/j.celrep.2016.01.077