scholarly journals Bigger Isn’t Always Better: Cell Size and the Spindle Assembly Checkpoint

2016 ◽  
Vol 36 (3) ◽  
pp. 244-246 ◽  
Author(s):  
Abigail R. Gerhold ◽  
Jean-Claude Labbé ◽  
Paul S. Maddox
2017 ◽  
Author(s):  
Abigail R. Gerhold ◽  
Vincent Poupart ◽  
Jean-Claude Labbé ◽  
Paul S. Maddox

AbstractThe spindle assembly checkpoint (SAC) is a conserved mitotic regulator that preserves genome stability. Despite its central role in preserving the fidelity of mitosis, the strength of the SAC varies widely between cell types. How the SAC is adapted to different cellular contexts remains largely unknown. Here we show that both cell size and cell fate impact SAC strength. While smaller cells have a stronger SAC, cells with a germline fate show increased SAC activity relative to their somatic counterparts across all cell sizes. We find that enhanced SAC activity in the germline blastomere P1 requires proper specification of cell fate downstream of the conserved PAR polarity proteins, supporting a model in which checkpoint factors are distributed asymmetrically during early germ cell divisions. Our results indicate that size scaling of SAC activity is modulated by cell fate and reveal a novel interaction between asymmetric cell division and the SAC.


2018 ◽  
Vol 29 (12) ◽  
pp. 1435-1448 ◽  
Author(s):  
Abigail R. Gerhold ◽  
Vincent Poupart ◽  
Jean-Claude Labbé ◽  
Paul S. Maddox

The spindle assembly checkpoint (SAC) is a conserved mitotic regulator that preserves genome stability by monitoring kinetochore–microtubule attachments and blocking anaphase onset until chromosome biorientation is achieved. Despite its central role in maintaining mitotic fidelity, the ability of the SAC to delay mitotic exit in the presence of kinetochore–microtubule attachment defects (SAC “strength”) appears to vary widely. How different cellular aspects drive this variation remains largely unknown. Here we show that SAC strength is correlated with cell fate during development of Caenorhabditis elegans embryos, with germline-fated cells experiencing longer mitotic delays upon spindle perturbation than somatic cells. These differences are entirely dependent on an intact checkpoint and only partially attributable to differences in cell size. In two-cell embryos, cell size accounts for half of the difference in SAC strength between the larger somatic AB and the smaller germline P1 blastomeres. The remaining difference requires asymmetric cytoplasmic partitioning downstream of PAR polarity proteins, suggesting that checkpoint-regulating factors are distributed asymmetrically during early germ cell divisions. Our results indicate that SAC activity is linked to cell fate and reveal a hitherto unknown interaction between asymmetric cell division and the SAC.


2020 ◽  
Vol 64 (2) ◽  
pp. 383-396
Author(s):  
Lara K. Krüger ◽  
Phong T. Tran

Abstract The mitotic spindle robustly scales with cell size in a plethora of different organisms. During development and throughout evolution, the spindle adjusts to cell size in metazoans and yeast in order to ensure faithful chromosome separation. Spindle adjustment to cell size occurs by the scaling of spindle length, spindle shape and the velocity of spindle assembly and elongation. Different mechanisms, depending on spindle structure and organism, account for these scaling relationships. The limited availability of critical spindle components, protein gradients, sequestration of spindle components, or post-translational modification and differential expression levels have been implicated in the regulation of spindle length and the spindle assembly/elongation velocity in a cell size-dependent manner. In this review, we will discuss the phenomenon and mechanisms of spindle length, spindle shape and spindle elongation velocity scaling with cell size.


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