Importin beta is a mitotic target of the small GTPase ran in spindle assembly

The GTPase Ran has recently been shown to stimulate microtubule polymerizat ion in mitotic extracts, but its mode of action is not understood. Here we show that the mitotic role of Ran is largely mediated by the nuclear transp ort factor importin beta. Importin beta inhibits spindle formation in vitro and in vivo and sequesters an aster promoting activity (APA) that consists of multiple, independent factors. One component of APA is the microtubule- associated protein NuMA. NuMA and other APA components are discharged from importin beta by RanGTP and induce spindle-like structures in the absence o f centrosomes, chromatin, or Ran. We propose that RanGTP functions in mitos is as in interphase by locally releasing cargoes from transport factors. In mitosis, this promotes spindle assembly by organizing microtubules in the vicinity of chromosomes.