Scaffolding a contractile ring
Anillin is a well-characterized scaffolding protein in cytokinesis and is a major focus of my third chapter where I demonstrate a new role for Anillin in regulating epithelial mechanics. During cell division, Anillin ensures successful cytokinesis by bundling filamentous-actin (F-actin), linking F-actin and Myosin II to the membrane, and regulating RhoA activity at the contractile ring \cite{Piekny_2010}. The N-terminal domains of Anillin participate in actomyosin binding/assembly, while the C-terminal domains include PH and C2 domains, which anchor it to the membrane, a RhoA binding domain, which allows it to interact with active RhoA, and binding sites for interacting with the GEF Ect2 and the GAPs MgcRacGAP and p190RhoGAP-A \cite{Piekny_2010,Frenette_2012,Manukyan_2014,Sun_2015}. Through direct binding to active RhoA, Anillin helps reset the clock on RhoA activation, acting as a buffer to extend the lifespan of active RhoA before passing it off downstream RhoA effectors \cite{Budnar_2018}. Early in cytokinesis, Anillin participates in a positive feedback loop in which its accumulation at the contractile ring is both dependent on and enhances Rho activation \cite{Piekny_2008}. Later in cytokinesis, it interacts with p190RhoGAP-A in a tension-sensitive manner, inactivating RhoA in response to excessive force \cite{Manukyan2014}. Finally, Anillin's bundling of F-actin also affects contractility in the ring where moderate levels of Anillin promotes efficient contraction of actomyosin \cite{Descovich_2017}. Thus, Anillin helps to promotes efficient contraction by fine-tuning RhoA signaling, bundling F-actin, and linking the contractile ring to the membrane.