NuSAP, a mitotic RanGTP target that stabilizes and cross-links microtubules

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Katharina Ribbeck - , European Molecular Biology Laboratory (EMBL) (Autor:in)
  • Aaron C. Groen - , Harvard University (Autor:in)
  • Rachel Santarella - , European Molecular Biology Laboratory (EMBL) (Autor:in)
  • Markus T. Bohnsack - , Ruprecht-Karls-Universität Heidelberg (Autor:in)
  • Tim Raemaekers - , KU Leuven (Autor:in)
  • Thomas Köcher - , Uppsala University (Autor:in)
  • Marc Gentzel - , European Molecular Biology Laboratory (EMBL) (Autor:in)
  • Dirk Görlich - , Ruprecht-Karls-Universität Heidelberg (Autor:in)
  • Matthias Wilm - , European Molecular Biology Laboratory (EMBL) (Autor:in)
  • Geert Carmeliet - , KU Leuven (Autor:in)
  • Timothy J. Mitchison - , Harvard University (Autor:in)
  • Jan Ellenberg - , European Molecular Biology Laboratory (EMBL) (Autor:in)
  • Andreas Hoenger - , University of Colorado Boulder (Autor:in)
  • Iain W. Mattaj - , European Molecular Biology Laboratory (EMBL) (Autor:in)

Abstract

Nucleolar and spindle-associated protein (NuSAP) was recently identified as a microtubule- and chromatin-binding protein in vertebrates that is nuclear during interphase. Small interfering RNA-mediated depletion of NuSAP resulted in aberrant spindle formation, missegregation of chromosomes, and ultimately blocked cell proliferation. We show here that NuSAP is enriched on chromatin-proximal microtubules at meiotic spindles in Xenopus oocytes. When added at higher than physiological levels to Xenopus egg extract, NuSAP induces extensive bundling of spindle microtubules and causes bundled microtubules within spindle-like structures to become longer. In vitro reconstitution experiments reveal two direct effects of NuSAP on microtubules: first, it can efficiently stabilize microtubules against depolymerization, and second, it can cross-link large numbers of microtubules into aster-like structures, thick fibers, and networks. With defined components we show that the activity of NuSAP is differentially regulated by Importin (Imp) α, Impβ, and Imp7. While Impα and Imp7 appear to block the microtubule-stabilizing activity of NuSAP, Impβ specifically suppresses aspects of the cross-linking activity of NuSAP. We propose that to achieve full NuSAP functionality at the spindle, all three importins must be dissociated by RanGTP. Once activated, NuSAP may aid to maintain spindle integrity by stabilizing and cross-linking microtubules around chromatin.

Details

OriginalspracheEnglisch
Seiten (von - bis)2646-2660
Seitenumfang15
FachzeitschriftMolecular Biology of the Cell
Jahrgang17
Ausgabenummer6
PublikationsstatusVeröffentlicht - Juni 2006
Peer-Review-StatusJa
Extern publiziertJa

Externe IDs

PubMed 16571672
ORCID /0000-0002-4482-6010/work/142251038

Schlagworte