Spatio-temporal Model for Silencing of Mitotic Spindle Assembly Checkpoints

Dr. Jian Liu
Investigator
Theoretical Cellular Physics
National Institutes of Health

Abstract: The spindle assembly checkpoint arrests mitotic progression until each kinetochore secures a stable attachment to the spindle. Despite fluctuating noise, this checkpoint remains robust and remarkably sensitive to even a single unattached kinetochore among many attached kinetochores; moreover, the checkpoint is silenced only after the final kinetochore-spindle attachment. Experimental observations have shown that checkpoint components stream from attached kinetochores along microtubules towards spindle poles. Here we incorporate this streaming behavior into a theoretical model that accounts for the robustness of checkpoint silencing. Poleward streams are integrated at spindle poles, but are diverted by any unattached kinetochore; consequently, accumulation of checkpoint components at spindle poles increases markedly only when every kinetochore is properly attached. This step change robustly triggers checkpoint silencing after, and only after, the final kinetochore-spindle attachment. Our model offers a conceptual framework that highlights the role of spatio-temporal regulation in mitotic spindle checkpoint signaling and fidelity of chromosome segregation.

Bio: Jian Liu graduated from Peking University with a B.S. in chemistry in 2000 and earned his Ph.D. in theoretical chemistry from the University of California, Berkeley in 2005. He completed postdoctoral fellowships at the University of California, San Diego, Center for Theoretical Biological Physics from 2005 to 2007 and at the University of California, Berkeley, Department of Molecular and Cell Biology in the laboratory of George Oster from 2007 to 2009. Dr. Liu joined the NHLBI as a tenure-track Investigator in 2009. Dr. Liu serves as a reviewer for the Journal of Chemical Physics, the Journal of Physical Chemistry, the Biophysical Journal, and Proceedings of the National Academy of Sciences.