Mechanics and regulation of cytokinesis

Abstract

Recent advances are revealing quantitative aspects of cytokinesis. Further, genetic analyses and cell imaging are providing insights into the molecular dynamics of cleavage furrow ingression as well as further refining our knowledge of the zones of the mitotic spindle that regulate the contractile properties of the overlying cortex. Ultimately, however, cortical mechanics are the result of signals that emanate from the mitotic spindle. A genuine quantitative understanding of cytokinesis must include a thorough analysis of the mechanical properties of the cortex and how signals modify these properties to dictate a well-controlled, error-free cytokinesis.

Figure 1

Diagram of the morphological changes of cytokinesis. The highly regimented nature of the shapes make cytokinesis a powerful model of cell shape change that is amenable to physical analyses. (a) The cell rounds up into a nearly spherical mother cell. (b) The cell elongates forming a cylindrical shape. (c) A furrow begins to ingress but maintains continuous curvature with the global cortex. (d) A discrete bridge forms that appears as a cylinder connecting the two daughter cells; the curvature of the bridge is discontinuous with the curvature of the two daughter cells. The bridge thins and lengthens. (e) The bridge is ultimately severed, producing two daughter cells. These shapes are highly stereotypical, at least for Dictyostelium. The cortical stretch modulus, S_c, is the viscoelasticity in the plane of the cortex. It is the energy cost for deforming the cell.

Figure 2

Amounts of wild-type myosin-II recruited to the cleavage furrow cortex follow predicted trends. Actual amounts of Dictyostelium myosin-II were measured using fluorescence ratio imaging microscopy. The predicted amounts were determined by considering the minimal force required to maintain cell shape and the biophysical properties and cellular concentration of Dictyostelium myosin-II. In contrast, 3xAla myosin-II continues to accumulate in the cleavage furrow cortex, probably because it is not subject to regulated disassemblyby myosin heavy chain kinase C.

Figure 3

The mitotic spindle provides spatio-temporal control of wild type cytokinesis. (a) Schematic relating spindle morphology and furrowing activity of wild type and Nedd-8 mutants. Red arrows indicate contractile activity. Black arrows represent positive signals that stimulate furrowing. Black inhibition bars indicate inhibitory signals that block ectopic furrow activity. (b) Summary of pathway of Nedd-8 control of ectopic furrowing through modulation of katanin and astral microtubules [33^•]. Rho also inhibits ectopic furrowing in mammalian cells [34].

Figure 4

Mitotic kinesin-like proteins localize to central spindle or midbody microtubules at different stages of cytokinesis. Three protein–protein interactions have been indicated to date. MKLP1 forms complexes with RhoGAPs, Cyk-4 and MgcRacGap. The CHO1 splice variant of MKLP1 includes an extra exon (exon 18), which encodes an actin binding domain. CHO1 can bind filamentous actin. MKLP1s also have a nucleotide-independent microtubule-binding site in their tail domain (not indicated). MKLP2 is phosphorylated by polo-like kinase 1 on multiple sites including a site in the neck linker. Phosphorylation of MKLP2’s neck linker site is required for polo-like kinase 1 to localize to the central spindle. The authors propose that polo-like kinase 1 binds the MKLP2 neck linker through its polo box domain for central spindle localization [42^•].