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???displayArticle.abstract??? Ran is a small GTP binding protein that was originally identified as a regulator of nucleocytoplasmic transport [1] and subsequently found to be important for spindle formation [2-5]. In mitosis, a gradient of Ran-GTP emanates from chromatin and diminishes toward spindle poles [6]. Ran-GTP promotes spindle self-organization through the release of importin-bound spindle assembly factors (SAFs), which stimulate microtubule (MT) nucleation and organization and regulate MT dynamics [7-9]. Although many SAFs are non-motile MT-associated proteins, such as NuMA, TPX2, and HURP [7, 10-12], Ran also controls motor proteins, including Kid and HSET/XCTK2 [13, 14]. The Kinesin-14 XCKT2 is important for spindle assembly and pole organization [15-20], and Ran-GTP is proposed to promote XCKT2 MT crosslinking activity by releasing importin α/β from a bipartite nuclear localization signal (NLS) located in the tail domain [14]. Here, we show that the Ran-GTP gradient spatially regulates XCTK2 within the spindle. A flattened Ran-GTP gradient blocked the ability of excess XCTK2 to stimulate bipolar spindle assembly and resulted in XCTK2-mediated bundling of free MTs. These effects required the XCTK2tail, which promoted the motility of XCTK2 within the spindle independent of the Ran-GTP gradient. In addition, the turnover kinetics of XCTK2 were spatially controlled: they were faster near the poles relative to the chromatin, but not with a mutant XCTK2 that cannot bind to importin α/β. Our results support a model in which the Ran-GTP gradient spatially coordinates motor localization with motility to ensure efficient spindle formation.
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Pubmed Braun,
The kinesin-14 Klp2 organizes microtubules into parallel bundles by an ATP-dependent sorting mechanism.
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Pubmed Cai,
Kinesin-14 family proteins HSET/XCTK2 control spindle length by cross-linking and sliding microtubules.
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Pubmed
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Xenbase Carazo-Salas,
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Xenbase Chandra,
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Xenbase Ems-McClung,
Importin alpha/beta and Ran-GTP regulate XCTK2 microtubule binding through a bipartite nuclear localization signal.
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Xenbase Fink,
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Pubmed Furuta,
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Pubmed Goshima,
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Pubmed Gruss,
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Xenbase Nachury,
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Xenbase Ohba,
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Xenbase Sharp,
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Pubmed Silljé,
HURP is a Ran-importin beta-regulated protein that stabilizes kinetochore microtubules in the vicinity of chromosomes.
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Pubmed Tao,
A homotetrameric kinesin-5, KLP61F, bundles microtubules and antagonizes Ncd in motility assays.
2006,
Pubmed Trieselmann,
Ran modulates spindle assembly by regulating a subset of TPX2 and Kid activities including Aurora A activation.
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Pubmed
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Xenbase Walczak,
XCTK2: a kinesin-related protein that promotes mitotic spindle assembly in Xenopus laevis egg extracts.
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Xenbase Walker,
ncd and kinesin motor domains interact with both alpha- and beta-tubulin.
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Pubmed Wiese,
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Xenbase Wittmann,
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Xenbase Yang,
Regional variation of microtubule flux reveals microtubule organization in the metaphase meiotic spindle.
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Xenbase
