Figure 2.

Depolymerization recruited by dynein-transported NuMA generates spindle poles. (A) NuMA (yellow) is transported to MT minus-ends by dynein (cyan). Oligomerization of NuMA leads to its accumulation at the spindle poles. (B) NuMA (yellow) recruits kinesin-13, whose binding (blue gradient) is spread among adjacent MTs. However, depolymerization (blue stars) only occurs at minus ends. Depolymerization is proportional to the amount of NuMA and inversely proportional to the local MT density (see Materials and methods). (C) Steady-state spindle structure with oligomerized NuMA (yellow) delivered to the pole by dynein (cyan). In the midzone, small amounts of kinesin-13 activity produce only slow depolymerization of minus ends. At the poles, accumulated NuMA recruits a large amount depolymerization activity distributed over few MTs, resulting in high depolymerization rates. (D) Minus-end density shows no polar accumulation (black) unless kinesin-13 depolymerization is added to the model (dark blue). With depolymerization, NuMA (light blue) accumulates at spindle poles (black arrows; average of 100, 95 simulations). (E) Schematic of metaphase steady state. MT density decreases from the midzone to the pole (green). Because depolymerization activity is spread over MTs, the depolymerization rate per MT increases with the distance from the midzone.

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