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Spindle Positioning

Groupleader: Dimitris Liakopoulos

The lab has moved to the Centre de Recherche de Biochimie Macromoléculaire (CRBM), an institute that belongs to the french National Research Center (Centre National de la Recherche Scientifique, CNRS), in Montpellier, France: http://www.crbm.cnrs.fr/

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How do polarized cells position their mitotic spindle at a specific place at a specific time?

During asymmetric cell division of polarized cells biomolecules are asymmetrically segregated between daughters. Asymmetric cell division is the main mode of division of stem cells and plays a central role in generating cell diversity during development. The position of the mitotic spindle within the cell determines whether the cell will divide symmetrically or asymmetrically. Spindle positioning in turn depends universally on interactions of astral microtubules (cMTs) with cortical factors. A complex network of proteins involving non-motor microtubule associated proteins (+TIPs), kinesins, dynein and actin-interacting proteins are involved in these interactions.

Budding yeast divides asymmetrically and is used as a model organism to study asymmetric divisions. Spindle positioning in yeast depends on two genetically identified pathways, comprising complexes of the microtubule-dependent motor dynein (dynein pathway) and the protein Kar9 (Kar9 pathway). The latter protein is the yeast functional equivalent of the Adenomatous Polyposis Coli (APC) tumor suppressor, a protein with a central role in spindle positioning from Drosophila to mammals. Dynein, Kar9 and APC homologues are universal mediators of spindle positioning during eukaryotic asymmetric division, but their regulation is poorly understood.

In the lab we explore how cell cycle regulators regulate temporal activation and dynamics of dynein and Kar9 complexes during spindle positioning in budding yeast. During transport along microtubules and interactions with cortical proteins these factors form highly dynamic protein complexes. Both formation of these complexes and coordination of their activity with other cytoskeletal events, like chromosome segregation and cytokinesis, are controlled by cyclin-dependent kinases. To understand the regulation of Kar9- and dynein complexes we use genetics to study their interactions. Using protein biochemistry, we analyze complex composition and phosphorylation. Finally, we use time-lapse fluorescence imaging and analysis to investigate complex dynamics in living yeast cells.

Download BZH Report Liakopoulos 2011-2013