Title: A study on the role of polarity, Rho family GTPases, and cell fate in cytokinesis
Description: Cytokinesis is the physical partition of one cell into two. In Chapter 1, I provide a brief introduction to cytokinesis and some of the proteins whose functions I parse out throughout my studies. In Chapter 2, I present work I’ve contributed to elucidate the role of polarity proteins in cytokinesis, as well as a look at the differential requirement for canonically essential cytokinetic proteins in the 4-cell embryo. In Chapter 3, I address a long-standing controversy in the field regarding the relationship between the Rac GAP protein Cyk-4 and the small GTPase Rac, and in particular the inhibitory role of Rac during cell division. My major body of work highlights the necessity not to close the books on the GAP activity of Cyk-4 and its inhibition of Rac. I show that Rac is unable to rescue cytokinesis failure in downstream Rho effectors whose loss weakens the contractile ring, suggesting it is not a promiscuous suppressor of cytokinesis. Additionally, I found that levels of non-muscle myosin-II and the actin binding domain of Utrophin were unchanged with loss of Cyk-4.

From this, I infer that Cyk-4 is unlikely to be an activator of the RhoGEF Ect-2. These results emphasize the need to probe further into the cross-talk between these GTPases. In chapter 4, I show inconclusive data addressing the role of cell fate signaling in protection against cytokinesis failure. Overall, this thesis represents my contributions to the field, revealing the complexity involved in assuring successful completion of cytokinesis.