EMBO Fellows Meeting 2012
EMBO Fellows Meeting 2012
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