A model for the regulatory network controlling the dynamics of kinetochore microtubule plus-ends and poleward flux in metaphase.
Tight regulation of kinetochore microtubule dynamics is required to generate the appropriate position and movement of chromosomes on the mitotic spindle. A widely studied but mysterious aspect of this regulation occurs during metaphase when polymerization of kinetochore microtubule plus-ends is balanced by depolymerization at their minus-ends. Thus, kinetochore microtubules maintain a constant net length, allowing chromosomes to persist at the spindle equator, but consist of tubulin subunits that continually flux toward spindle poles. Here, we construct a feasible network of regulatory proteins for controlling kinetochore microtubule plus-end dynamics, which was combined with a Monte Carlo algorithm to simulate metaphase tubulin flux. We also test the network model by combining it with a force-balancing model explicitly taking force generators into account. Our data reveal how relatively simple interrelationships among proteins that stimulate microtubule plus-end polymerization, depolymerization, and dynamicity can induce robust flux while accurately predicting apparently contradictory results of knockdown experiments. The model also provides a simple and robust physical mechanism through which the regulatory networks at kinetochore microtubule plus- and minus-ends could communicate.
Fernandez
Nicolas
N
Department of Physiology and Biophysics, Albert Einstein College of Medicine of Yeshiva University, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Chang
Qiang
Q
Buster
Daniel W
DW
Sharp
David J
DJ
Ma
Ao
A
D000465:Algorithms; D000818:Animals; D003198:Computer Simulation; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism; D016547:Kinesins / Q000378:metabolism; D018386:Kinetochores / Q000378:metabolism*; D008677:Metaphase; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism*; D008938:Mitosis; D008954:Models, Biological; D015233:Models, Statistical; D034622:RNA Interference; D008941:Spindle Apparatus / Q000378:metabolism
D029721:Drosophila Proteins; D008869:Microtubule-Associated Proteins; C481338:Klp59C protein, Drosophila; D016547:Kinesins