The Ran GTPase regulates mitotic spindle assembly

Ran is an abundant nuclear GTPase with a clear role in nuclear transport du ring interphase [1] but with roles in mitotic regulation that are less well understood [2], The nucleotide-binding state of Ran is regulated by a GTPa se activating protein, RanGAP1, and by a guanine nucleotide exchange factor , RCC1, Ran also interacts with a guanine nucleotide dissociation inhibitor , RanBP1, RanBP1 has a high affinity for GTP-bound Ran, and it acts as a co factor for RanGAP1, increasing the rate of GAP-mediated GTP hydrolysis on R an approximately tenfold [3]. RanBP1 levels oscillate during the cell cycle [4], and increased concentrations of RanBP1 prolong mitosis in mammalian c ells [4] and in Xenopus egg extracts (our unpublished observations). We inv estigated how increased concentrations of RanBP1 disturb mitosis, We found that spindle assembly is dramatically disrupted when exogenous RanBP1 is ad ded to M phase Xenopus egg extracts. We present evidence that the role of R an in spindle assembly is independent of nuclear transport and is probably mediated through changes in microtubule dynamics.