UC San Diego
Signaling from the asters and spindle midzone is required to promote cytokinesis in the early C. elegans embryo
- Author(s): Lewellyn, Lindsay Kyle
- et al.
Cytokinesis is the final step of the cell division that physically separates a single cell into two daughter cells following chromosome segregation. In order to insure that each daughter cell receives the proper genetic complement, cytokinesis must be both spatially and temporally coupled to chromosome segregation. Cytokinesis is accomplished by formation and constriction of a contractile ring made up of actin, myosin, anillin, and the septins. One of the critical questions in the field is how does the cell maintain precise spatial and temporal control over the assembly and constriction of the contractile ring? Although the precise molecular signals are still being debated, it is known that signals from the anaphase spindle are critical for furrow formation and ingression. Using the early C. elegans embryo I have found that integration of signals from astral microtubules and the spindle midzone is critical for the formation of a single furrow during cytokinesis. During early anaphase, astral microtubules provide an inhibitory signal to prevent accumulation of contractile ring proteins in the anterior and posterior of the cell, leading to their enrichment in the equatorial region. Proper separation of the asters is important for this early signal, since delaying or preventing aster separation disrupts the equatorial enrichment of anillin and myosin and delays furrow formation. Following this initial signal from the astral microtubules, a positive signal from the midzone - mediated by Centralspindlin and the Chromosomal Passenger Complex (CPC) - drives furrow ingression and completion. Although the initial patterning of contractility and the timing of furrow formation are unaffected, depletion of Centralspindlin or the CPC leads to a decrease in the rate of ingression and failure of cytokinesis. My work has also shown that Centralspindlin and the CPC are involved in distinct pathways to promote furrow ingression. The key role of the Centralspindlin complex is to inactivate the small GTPase, Rac, whereas the role of the CPC is likely through promoting contractile ring disassembly through regulation of anillin and/or septin