Ran induces spindle assembly by reversing the inhibitory effect of importin alpha on TPX2 activity

The small GTPase Ran, bound to GTP, is required for the induction of spindl e formation by chromosomes in M phase. High concentrations of Ran.GTP are p roposed to surround M phase chromatin. We show that the action of Ran.GTP i n spindle formation requires TPX2, a microtubule-associated protein previou sly known to target a motor protein, Xklp2, to microtubules. TPX2 is normal ly inactivated by binding to the nuclear import factor, importin alpha, and is displaced from importin alpha by the action of Ran.GTP. TPX2 is require d for Ran.GTP and chromatin-induced microtubule assembly in M phase extract s and mediates spontaneous microtubule assembly when present in excess over free importin alpha. Thus, components of the nuclear transport machinery s erve to regulate spindle formation in M phase.