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Asymmetry of the Budding Yeast Tem1 GTPase at Spindle Poles Is Required for Spindle Positioning But Not for Mitotic Exit


In asymmetrically dividing cells, proper positioning of the mitotic spindle relative to polarity determinants is crucial to ensure the unequal fate of daughter cells. In stem cells, derangement of the mechanisms controlling asymmetric cell division, including spindle positioning, affects the developmental fate of daughter cells and can promote tumourigenesis. The budding yeast Saccharomyces cerevisiae is an outstanding model system to study spindle positioning and its links with cell cycle progression. Indeed, budding yeast has redundant mechanisms driving spindle positioning and a “spindle position checkpoint” (SPOC) that delays cell division whenever the spindle is not properly aligned. The target of the SPOC is the small GTPase Tem1 that controls both spindle positioning and mitotic exit and whose activity can be inhibited by the GTPase-activating protein Bub2/Bfa1. Tem1, Bub2 and Bfa1 form a complex at spindle poles that becomes asymmetric and accumulates on one spindle pole when the spindle is properly aligned, while it remains symmetric in case of spindle mispositioning. Through expression of several mutant or chimeric proteins leading to symmetric distribution of the Bub2/Bfa1/Tem1 complex, we establish that asymmetry of these proteins does not drive mitotic exit but rather it contributes to spindle alignment.


Vyšlo v časopise: Asymmetry of the Budding Yeast Tem1 GTPase at Spindle Poles Is Required for Spindle Positioning But Not for Mitotic Exit. PLoS Genet 11(2): e32767. doi:10.1371/journal.pgen.1004938
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004938

Souhrn

In asymmetrically dividing cells, proper positioning of the mitotic spindle relative to polarity determinants is crucial to ensure the unequal fate of daughter cells. In stem cells, derangement of the mechanisms controlling asymmetric cell division, including spindle positioning, affects the developmental fate of daughter cells and can promote tumourigenesis. The budding yeast Saccharomyces cerevisiae is an outstanding model system to study spindle positioning and its links with cell cycle progression. Indeed, budding yeast has redundant mechanisms driving spindle positioning and a “spindle position checkpoint” (SPOC) that delays cell division whenever the spindle is not properly aligned. The target of the SPOC is the small GTPase Tem1 that controls both spindle positioning and mitotic exit and whose activity can be inhibited by the GTPase-activating protein Bub2/Bfa1. Tem1, Bub2 and Bfa1 form a complex at spindle poles that becomes asymmetric and accumulates on one spindle pole when the spindle is properly aligned, while it remains symmetric in case of spindle mispositioning. Through expression of several mutant or chimeric proteins leading to symmetric distribution of the Bub2/Bfa1/Tem1 complex, we establish that asymmetry of these proteins does not drive mitotic exit but rather it contributes to spindle alignment.


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