Click here to close Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly. We suggest using a current version of Chrome, FireFox, or Safari.
XB-ART-53279
Curr Biol 2015 Jun 01;2511:1509-14. doi: 10.1016/j.cub.2015.04.015.
Show Gene links Show Anatomy links

The Ran-GTP gradient spatially regulates XCTK2 in the spindle.

Weaver LN , Ems-McClung SC , Chen SH , Yang G , Shaw SL , Walczak CE .


???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 XCTK2 tail, 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.

???displayArticle.pubmedLink??? 25981788
???displayArticle.pmcLink??? PMC4452415
???displayArticle.link??? Curr Biol
???displayArticle.grants??? [+]

Species referenced: Xenopus
Genes referenced: dlgap5 kif22 kifc1 numa1 ran tpx2

References [+] :
Bischoff, RanGAP1 induces GTPase activity of nuclear Ras-related Ran. 1994, Pubmed