Abstract
In cells, a complex network of microtubule-associated-proteins regulates the dynamic growth and shrinkage of microtubules that is essential for division and migration. In vitro approaches with purified components have helped to elucidate the mechanisms and the effects of individual microtubule plus-end-localizing proteins (+TIPs) on microtubule dynamics. Because microtubule dynamics observed in vitro with individual +TIPs does not account for the dynamics observed in vivo, it is important to study the combined effects of +TIPs. Here we show that two well-studied +TIPs - microtubule plus-end-tracking protein EB1, and the microtubule polymerase XMAP215 - act together to strongly promote microtubule growth to rates never before observed with purified proteins. Unexpectedly, we find that the combined effects of XMAP215 and EB1 are highly synergistic, with acceleration of growth well beyond the product of the individual effects of either protein. The synergy remains after EB1's C-terminal 20 amino acids have been removed, showing that it does not rely on any of the canonical EB1 interactions. The increase in growth rates is accompanied by a strong enhancement of microtubule catastrophe, thereby rendering the fast and dynamic microtubule behavior typically observed in cells.
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