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CAUDRON/AAAS! m) `& \1 Q* `% `+ [% v
c+ A5 i- l8 `) I9 fOne 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.; ]6 A) L# f8 w
+ `/ B! h+ L0 IChromatin 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.
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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 R) u; ~5 C' Y$ s3 E/ e
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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.
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y& X( T; \; F: b3 O4 W2 s% _: bOne 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.. o" Y1 g5 _1 Y9 b! I! i
( W7 p- ]& |. g$ t% E' a `" O+ vThe 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.
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Reference:9 v* h2 u0 r' y
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Caudron, 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
