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Title: Adhesion-dependent cell division
Author: Dix, Christina Lyn
ISNI:       0000 0004 7230 5831
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2018
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Animal cells undergo a dramatic series of cell shape changes as they pass through mitosis and divide which depend both on remodelling of the contrac- tile actomyosin cortex and on the release of cell-substrate adhesions. Here, I use the adherent, non-transformed, human RPE1 cell line as a model system in which to explore the dynamics of these shape changes, and the function of mitotic adhesion remodelling. Although these cells are highly motile, and therefore polarised in interphase, many pause migration and elongate to be- come bipolar prior to mitosis. Interestingly, and in contrast to most reported cell types, these cells do not round fully, and many leave long adhesive tails con- nected to the underlying substrate. These are typically bipolar, persist through- out mitosis, and guide cell respreading following mitotic exit. Further analysis shows that while many proteins are lost from focal adhesion complexes during mitotic rounding, integrin-rich contacts remain in place along these tails as well as defining the tips of retraction fibres. These adhesions are functionally impor- tant in RPE1 cells, since these cells fail to divide when removed from the sub- strate prior to entry into mitosis. The restoration of cell-substrate adhesions at anaphase are sufficient to rescue division in control cells. However, adhesions must persist into mitotic exit for division in cells compromised in their ability to construct an actomyosin ring. Division in these cells depends on respreading, since Ect2 RNAi cells fail to divide on small adhesive islands, but successfully divide on larger patterns with the cytoplasmic bridge connecting daughter cells narrowing as they migrate away from one another. Together these results re- veal the importance of coupling adhesion remodeling to mitotic progression.
Supervisor: Baum, B. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available