Importin beta is a mitotic target of the small GTPase Ran in spindle assembly.
The GTPase Ran has recently been shown to stimulate microtubule polymerization 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 transport 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 of centrosomes, chromatin, or Ran. We propose that RanGTP functions in mitosis as in interphase by locally releasing cargoes from transport factors. In mitosis, this promotes spindle assembly by organizing microtubules in the vicinity of chromosomes.
Nachury
M V
MV
Department of Molecular and Cell Biology, Division of Cell and Developmental Biology, University of California-Berkeley, Berkeley, CA 94720, USA.
Maresca
T J
TJ
Salmon
W C
WC
Waterman-Storer
C M
CM
Heald
R
R
Weis
K
K
D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology; D028884:Karyopherins; D008322:Mammals; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism*; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism*; D014981:Xenopus; D029867:Xenopus Proteins; D020931:ran GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
D028884:Karyopherins; C489079:NUMA1 protein, Xenopus; D009687:Nuclear Proteins; D029867:Xenopus Proteins; D020558:GTP Phosphohydrolases; D020931:ran GTP-Binding Protein