Rob Cross

TACC proteins play a crucial but as yet poorly understood role in the spatiotemporal control of microtubule assembly, and specifically in mitotic spindle assembly. Alp7 is an S. pombe TACC that binds tightly to Alp14, thought to be a tip-tracking microtubule polymerase, and carries it into the nucleus at the onset of mitosis. Using in vitroreconstitution, we have recently found that Alp7 dramatically enhances the processivity of Alp14 at the growing plus end tips of dynamic S. pombe microtubules, suppressing catastrophe and driving sustained accelerated growth for up to several minutes at up to 10x wild type rates. Remarkably, the ability of Alp7-Alp14 to accelerate microtubule growth is completely blocked by adding 5% brain tubulin to the dynamic S. pombe microtubules. This observation of powerful pseudosubstrate inhibition is consistent with a model in which Alp7-Alp14 acts as a classical catalyst to accelerate both the on- and off-rates for GTP-tubulin at the plus ends of dynamic microtubules


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