First published online November 3, 2003
Journal of Cell Science 116, e2304 (2003)
Copyright © 2003 The Company of Biologists Limited
Importin mechanisms
The small GTPase Ran regulates nucleocytoplasmic trafficking by binding to importin nuclear transport receptors, causing them to release cargo. Ran also regulates assembly of the mitotic spindle. It is thought to do so by a similar mechanism, preventing importins from interacting with and inhibiting spindle assembly factors. Andrew Wilde and co-workers have now directly tested this hypothesis by analysing interactions between importin and two proteins: the known Ran pathway target TPX2, a spindle-assembly factor that recruits the kinase Aurora A (essential for spindle assembly); and Kid, a kinesin involved in mitotic chromosome orientation (see p. 4791). Using deletion analyses, the authors define the nuclear localization (importin-binding), microtubule-binding and Aurora-A-binding sequences in TPX-2. They go on to demonstrate that binding of importin to TPX2 inhibits its interaction with Aurora A but not microtubules. A similar approach reveals that importin can bind to Kid, which disrupts its interaction with microtubules but not DNA. The authors findings indicate that Ran signalling regulates spindle assembly factors by affecting a subset of their activities. Moreover, they pinpoint Kid - and hence chromosome alignment - as a novel downstream target of the pathway.
Related articles in JCS:
- Ran modulates spindle assembly by regulating a subset of TPX2 and Kid activities including Aurora A activation
- Nadia Trieselmann, Sheri Armstrong, Jennifer Rauw, and Andrew Wilde
JCS 2003 116: 4791-4798.
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