Cell Reports
Volume 1, Issue 5, 31 May 2012, Pages 408-416
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The Functional Antagonism between Eg5 and Dynein in Spindle Bipolarization Is Not Compatible with a Simple Push-Pull Model

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Summary

During cell division, the molecular motor Eg5 crosslinks overlapping antiparallel microtubules and pushes them apart to separate mitotic spindle poles. Dynein has been proposed as a direct antagonist of Eg5 at the spindle equator, pulling on antiparallel microtubules and favoring spindle collapse. Some of the experiments supporting this hypothesis relied on endpoint quantifications of spindle phenotypes rather than following individual cell fates over time. Here, we present a mathematical model and proof-of-principle experiments to demonstrate that endpoint quantifications can be fundamentally misleading because they overestimate defective phenotypes. Indeed, live-cell imaging reveals that, while depletion of dynein or the dynein binding protein Lis1 enables spindle formation in presence of an Eg5 inhibitor, the activities of dynein and Eg5 cannot be titrated against each other. Thus, dynein most likely antagonizes Eg5 indirectly by exerting force at different spindle locations rather than through a simple push-pull mechanism at the spindle equator.

Highlights

► Fixed-cell microscopy images overestimate the frequency of defective mitotic spindles ► Live-cell-imaging-based conclusions often contradict results from fixed samples ► Antagonizing mitotic spindle motor activities of dynein and Eg5 are not titratable ► Spindle dynein-Eg5 antagonism is incompatible with a simple push-pull mechanism

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Present address: Department of Systems Biology, Harvard Medical School, 200 Longwood Avenue, Warren Alpert Building 536, Boston, MA 02115, USA