Abstract
SummaryIn anaphase spindles, antiparallel microtubules associate to form tight midzone bundles, as required for functional spindle architecture and correct chromosome segregation. Several proteins selectively bind to these overlaps to control cytokinesis. How midzone bundles assemble is poorly understood. Here, using an in vitro reconstitution approach, we demonstrate that minimal midzone bundles can reliably self-organize in solution from dynamic microtubules, the microtubule crosslinker PRC1, and the motor protein KIF4A. The length of the central antiparallel overlaps in these microtubule bundles is similar to that observed in cells and is controlled by the PRC1/KIF4A ratio. Experiments and computer simulations demonstrate that minimal midzone bundle formation results from promoting antiparallel microtubule crosslinking, stopping microtubule plus-end dynamicity, and motor-driven midzone compaction and alignment. The robustness of this process suggests that a similar self-organization mechanism may contribute to the reorganization of the spindle architecture during the metaphase to anaphase transition in cells.
Highlights
During mitosis, the microtubule cytoskeleton forms a bipolar spindle around chromosomes
Using an in vitro reconstitution approach, we demonstrate that minimal midzone bundles can reliably self-organize in solution from dynamic microtubules, the microtubule crosslinker PRC1, and the motor protein KIF4A
The length of the central antiparallel overlaps in these microtubule bundles is similar to that observed in cells and is controlled by the PRC1/KIF4A ratio
Summary
The microtubule cytoskeleton forms a bipolar spindle around chromosomes. A critical player is PRC1 (protein required for cytokinesis 1) [5,6,7,8], which is conserved within metazoans, plants, and yeast [9,10,11,12,13]. It preferentially crosslinks antiparallel microtubules and recruits other anaphase spindle proteins [14,15,16,17]. PRC1 is a homodimer and binds microtubules with its spectrin domains and neighboring unstructured positively charged regions, keeping antiparallel microtubules separated by $35 nm (compared to an outer microtubule diameter of 25 nm; Figure 1A) [14, 17,18,19]
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