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CAUDRON/AAAS
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, K8 H+ w) B5 wOne RanGTP gradient builds on another to spatially guide mitotic spindle assembly, say Ma?wen Caudron, Eric Karsenti (European Molecular Biology Laboratory, Heidelberg, Germany), and colleagues.* P5 v) b0 s6 j* }7 N( S
7 N1 X: j1 ]& p: E6 P4 kChromatin was known to promote spindle assembly via its effects on the Ran GTPase. RanGTP is abundant near chromosomes due to activation by a Ran–guanosine nucleotide exchange factor localized on chromosomes, but the extent of RanGTP localization and its function remained unknown. "Researchers suspected that long-range spindle effects were being mediated by chromosomes, but they couldn't prove this for certain," says Karsenti.& q- _( G. w N( y) Z
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Combining mathematical modeling and fluorescent microscopy, Karsenti's group now shows that RanGTP diffusion away from chromosomes creates an interrelated series of short- and long-range protein gradients. The gradient of free RanGTP is very steep, but built upon it are shallower gradients of RanGTP–importin ? and RanGTP–importin ?–RanBP1. The RanGTP–importin ? complex helps build the spindle. But binding of RanBP1 to RanGTP–importin ? inactivates the complex.4 n+ C9 `1 {0 k4 p# S, d% v2 e3 F7 S
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This inactivation helps shape the RanGTP–importin ? gradient. It is the RanGTP–importin ? that ultimately promotes two different behaviors: microtubule nucleation at chromosomes; and stabilization of growing tubules within the spindle. It does so by activating the release of nuclear localization signal (NLS)-containing proteins that regulate microtubules. "It is really the free NLS proteins that are important for driving spindle formation," says Karsenti.* \5 X7 [6 |! _( R. u
( g: U; l2 Y( L l3 MOne NLS protein, TPX2, facilitates microtubule nucleation in an all-or-nothing manner that occurs only when the amount of RanGTP–importin ? is above a certain threshold〞that is, right around chromosomes. Release of another yet-unidentified NLS protein increases linearly with RanGTP–importin ? concentrations and promotes microtubule stabilization. Thus, microtubules emanating from centrosomes become increasingly stabilized the closer they get to chromosomes.% y+ d/ p+ J- _
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The next goal in Karsenti's view is to identify the NLS protein gradients to better understand how they promote local nucleation and biased microtubule growth toward chromosomes.$ R2 L _( b% O6 R
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Reference:
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" A" q' a# {- y' s- RCaudron, M., et al. 2005. Science. 309:1373–1376.(The RanGTP-importin ? gradient (red) pro) |
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发表于 2009-3-6 09:06
发表于 2015-5-22 14:16
