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J Cell Biol January 1, 2020; 219 (2):

RanGTP induces an effector gradient of XCTK2 and importin α/β for spindle microtubule cross-linking.

Ems-McClung SC , Emch M , Zhang S , Mahnoor S , Weaver LN , Walczak CE .

High RanGTP around chromatin is important for governing spindle assembly during meiosis and mitosis by releasing the inhibitory effects of importin α/β. Here we examine how the Ran gradient regulates Kinesin-14 function to control spindle organization. We show that Xenopus Kinesin-14, XCTK2, and importin α/β form an effector gradient that is highest at the poles and diminishes toward the chromatin, which is opposite the RanGTP gradient. Importin α and β preferentially inhibit XCTK2 antiparallel microtubule cross-linking and sliding by decreasing the microtubule affinity of the XCTK2 tail domain. This change in microtubule affinity enables RanGTP to target endogenous XCTK2 to the spindle. We propose that these combined actions of the Ran pathway are critical to promote Kinesin-14 parallel microtubule cross-linking to help focus spindle poles for efficient bipolar spindle assembly. Furthermore, our work illustrates that RanGTP regulation in the spindle is not simply a switch, but rather generates effector gradients where importins α and β gradually tune the activities of spindle assembly factors.

PubMed ID: 31865374
PMC ID: PMC7041689
Article link: J Cell Biol
Grant support: [+]

Species referenced: Xenopus
Genes referenced: kif14 kifc1 kpna1 numa1 ran
GO keywords: cytoskeleton [+]

Article Images: [+] show captions
References [+] :
Athale, Regulation of microtubule dynamics by reaction cascades around chromosomes. 2008, Pubmed, Xenbase