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EMBO Fellows Meeting 2012

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Sachin Kotak<br />

<strong>EMBO</strong> <strong>Fellows</strong> <strong>Meeting</strong> <strong>2012</strong><br />

Cortical dynein is critical for directing spindle positioning in human cells<br />

Abstract<br />

Correct spindle positioning is fundamental for proper cell division during metazoan development and stem cell<br />

lineages. Studies in several cellular systems revealed that dynein and an evolutionarily conserved ternary<br />

complex (LIN-5/GPR-1/2/Gα in C. elegans and NuMA/LGN/Gα in human cells) are required for correct spindle<br />

positioning, but their relationship remains incompletely understood. By analyzing fixed specimens on<br />

fibronectin-coated coverslips and conducting live imaging experiments, we uncover that balance levels of<br />

ternary complex components are critical for dynein-dependent spindle positioning in non-polarized HeLa cells<br />

and C.elegans embryos. Moreover, using mutant versions of Gα, we establish that dynein is needed at the<br />

plasma membrane to direct spindle positioning Importantly, we identified a region within NuMA that mediates<br />

association with dynein. By targeting this region to the plasma membrane, we demonstrate that the mere<br />

presence of dynein at that location is sufficient to direct spindle oscillations in HeLa cells. Overall, our findings<br />

support a model in which the balanced proportion of ternary complex serves to anchor dynein at the plasma<br />

membrane to direct spindle positioning.<br />

Sachin Kotak and Pierre Gönczy<br />

Swiss Institute for Experimental Cancer Research (ISREC)<br />

School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland<br />

14-17 June <strong>2012</strong>, Heidelberg, Germany

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