RanGTP induces an effector gradient of XCTK2 and importin alpha/beta for spindle microtubule cross-linking

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Ems-McClung S. C., Emch M., Zhang S., Mahnoor S., Weaver L. N., Walczak C. E.

JOURNAL OF CELL BIOLOGY, cilt.219, sa.2, 2020 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 219 Sayı: 2
  • Basım Tarihi: 2020
  • Doi Numarası: 10.1083/jcb.201906045
  • Dergi Adı: JOURNAL OF CELL BIOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Agricultural & Environmental Science Database, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE
  • Orta Doğu Teknik Üniversitesi Adresli: Hayır

Özet

High RanGTP around chromatin is important for governing spindle assembly during meiosis and mitosis by releasing the inhibitory effects of importin alpha/beta Here we examine how the Ran gradient regulates Kinesin-14 function to control spindle organization. We show that Xenopus Kinesin-14, XCTK2, and importin alpha/beta form an effector gradient that is highest at the poles and diminishes toward the chromatin, which is opposite the RanGTP gradient. Importin alpha and beta 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 alpha and beta gradually tune the activities of spindle assembly factors.