Kalab P, Pu R T, Dasso M
Laboratory of Molecular Embryology NICHD NIH Building 18, Room 106, Bethesda, Maryland, 20892-5431, USA.
Curr Biol. 1999 May 6;9(9):481-4. doi: 10.1016/s0960-9822(99)80213-9.
Ran is an abundant nuclear GTPase with a clear role in nuclear transport during interphase but with roles in mitotic regulation that are less well understood. The nucleotide-binding state of Ran is regulated by a GTPase 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 cofactor for RanGAP1, increasing the rate of GAP-mediated GTP hydrolysis on Ran approximately tenfold. RanBP1 levels oscillate during the cell cycle [4], and increased concentrations of RanBP1 prolong mitosis in mammalian cells and in Xenopus egg extracts (our unpublished observations). We investigated how increased concentrations of RanBP1 disturb mitosis. We found that spindle assembly is dramatically disrupted when exogenous RanBP1 is added to M phase Xenopus egg extracts. We present evidence that the role of Ran in spindle assembly is independent of nuclear transport and is probably mediated through changes in microtubule dynamics.
Ran是一种丰富的核GTP酶，在间期的核运输中具有明确作用，但在有丝分裂调控中的作用尚不太清楚。Ran的核苷酸结合状态受GTP酶激活蛋白RanGAP1和鸟嘌呤核苷酸交换因子RCC1的调节。Ran还与鸟嘌呤核苷酸解离抑制剂RanBP1相互作用。RanBP1对结合GTP的Ran具有高亲和力，并且它作为RanGAP1的辅因子，将Ran上由GAP介导的GTP水解速率提高约十倍。RanBP1水平在细胞周期中振荡[4]，并且RanBP1浓度的增加会延长哺乳动物细胞和非洲爪蟾卵提取物中的有丝分裂（我们未发表的观察结果）。我们研究了RanBP1浓度增加如何扰乱有丝分裂。我们发现，当将外源RanBP1添加到M期非洲爪蟾卵提取物中时，纺锤体组装会受到显著破坏。我们提供的证据表明，Ran在纺锤体组装中的作用独立于核运输，并且可能是通过微管动力学的变化介导的。
