The Ran-GTP gradient spatially regulates XCTK2 in the spindle

Lesley N. Weaver, Stephanie C. Ems-Mcclung, Sez Hon R Chen, Ge Yang, Sidney L. Shaw, Claire Walczak

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Summary 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.

Original languageEnglish (US)
Pages (from-to)1509-1514
Number of pages6
JournalCurrent Biology
Volume25
Issue number11
DOIs
StatePublished - Jun 1 2015

Fingerprint

importins
Guanosine Triphosphate
microtubules
Karyopherins
chromatin
Microtubules
Spindle Poles
tail
nucleocytoplasmic transport
Poles
nuclear localization signals
kinesin
Chromatin
G-proteins
crosslinking
mitosis
proteins
Kinesin
Nuclear Localization Signals
Microtubule-Associated Proteins

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Weaver, L. N., Ems-Mcclung, S. C., Chen, S. H. R., Yang, G., Shaw, S. L., & Walczak, C. (2015). The Ran-GTP gradient spatially regulates XCTK2 in the spindle. Current Biology, 25(11), 1509-1514. https://doi.org/10.1016/j.cub.2015.04.015

The Ran-GTP gradient spatially regulates XCTK2 in the spindle. / Weaver, Lesley N.; Ems-Mcclung, Stephanie C.; Chen, Sez Hon R; Yang, Ge; Shaw, Sidney L.; Walczak, Claire.

In: Current Biology, Vol. 25, No. 11, 01.06.2015, p. 1509-1514.

Research output: Contribution to journalArticle

Weaver, LN, Ems-Mcclung, SC, Chen, SHR, Yang, G, Shaw, SL & Walczak, C 2015, 'The Ran-GTP gradient spatially regulates XCTK2 in the spindle', Current Biology, vol. 25, no. 11, pp. 1509-1514. https://doi.org/10.1016/j.cub.2015.04.015
Weaver LN, Ems-Mcclung SC, Chen SHR, Yang G, Shaw SL, Walczak C. The Ran-GTP gradient spatially regulates XCTK2 in the spindle. Current Biology. 2015 Jun 1;25(11):1509-1514. https://doi.org/10.1016/j.cub.2015.04.015
Weaver, Lesley N. ; Ems-Mcclung, Stephanie C. ; Chen, Sez Hon R ; Yang, Ge ; Shaw, Sidney L. ; Walczak, Claire. / The Ran-GTP gradient spatially regulates XCTK2 in the spindle. In: Current Biology. 2015 ; Vol. 25, No. 11. pp. 1509-1514.
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