Dynein Antagonizes Eg5 by Crosslinking and Sliding Antiparallel Microtubules

Nick P. Ferenz, Raja Paul, Carey Fagerstrom, Alex Mogilner, Patricia Wadsworth

Research output: Contribution to journalArticle

68 Scopus citations

Abstract

Mitotic spindle assembly requires the combined activity of various molecular motor proteins, including Eg5 [1] and dynein [2]. Together, these motors generate antagonistic forces during mammalian bipolar spindle assembly [3]; what remains unknown, however, is how these motors are functionally coordinated such that antagonism is possible. Given that Eg5 generates an outward force by crosslinking and sliding apart antiparallel microtubules (MTs) [4-6], we explored the possibility that dynein generates an inward force by likewise sliding antiparallel MTs. We reasoned that antiparallel overlap, and therefore the magnitude of a dynein-mediated force, would be inversely proportional to the initial distance between centrosomes. To capitalize on this relationship, we utilized a nocodazole washout assay to mimic spindle assembly. We found that Eg5 inhibition led to either monopolar or bipolar spindle formation, depending on whether centrosomes were initially separated by less than or greater than 5.5 μm, respectively. Mathematical modeling predicted this same spindle bistability in the absence of functional Eg5 and required dynein acting on antiparallel MTs to do so. Our results suggest that dynein functionally coordinates with Eg5 by crosslinking and sliding antiparallel MTs, a novel role for dynein within the framework of spindle assembly.

Original languageEnglish (US)
Pages (from-to)1833-1838
Number of pages6
JournalCurrent Biology
Volume19
Issue number21
DOIs
StatePublished - Nov 17 2009

Keywords

  • CELLBIO

ASJC Scopus subject areas

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

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    Ferenz, N. P., Paul, R., Fagerstrom, C., Mogilner, A., & Wadsworth, P. (2009). Dynein Antagonizes Eg5 by Crosslinking and Sliding Antiparallel Microtubules. Current Biology, 19(21), 1833-1838. https://doi.org/10.1016/j.cub.2009.09.025