Cell division, also known as cytokinesis, is the last step of mitosis and describes the process where an actin-myosin contractile ring pinches in the cortex and cytosol to form two daughter cells. Cytokinesis is regulated by the small GTPase RhoA, which is activated by the GEF (guanine nucleotide exchange factor) Ect2 in anaphase (see figure below). Ect2 is recruited to the central spindle and overlying cortex via centralspindlin (MgcRacGAP/Cyk4 and MKLP1) to ensure that contractile ring formation is coupled with the segregation of sister chromatids. To form the contractile ring, RhoA-GTP activates Rho-dependent kinase (ROCK), which phosphorylates non-muscle myosin regulatory light chain to promote the assembly and activity of bipolar myosin filaments. RhoA-GTP also activates formins, which promote polymerization of F-actin filaments. Furthermore, active RhoA recruits the scaffolding protein anillin, which binds to actin and myosin by its N-terminus, and to membrane-associated septins via its C-terminus. Septins are GTP-binding proteins that form hetero-oligomeric complexes in the form of filaments or rings. It is not clear how these filamentous proteins are assembled into the ring, but their function likely is to crosslink the contractile apparatus to the overlying plasma membrane. The mechanism of ring constriction may occur by the myosin-mediated sliding and/or crosslinking of anti-parallel F-actin filaments, which progressively closes the ring and simultaneously pulls in the membrane to pinch the cell in two.
To get a better understanding of how the division plane is determined, and maintained during cytokinesis, we are currently investigating how microtubules, chromatin and the cortex are coordinated for this process in HeLa and Madin-Darby Canine Kidney (MDCK) epithelial cells.
Piekny et al., 2005, Trends Cell Biol