Crosslinkers both drive and brake cytoskeletal remodeling and furrowing in cytokinesis

Abstract

Cytokinesis and other cell shape changes are driven by the actomyosin contractile cytoskeleton.The molecular rearrangements that bring about contractility in non-muscle cells are currently debated. Specifically, both filament sliding by myosin motors, as well as cytoskeletal crosslinking by myosins and non-motor crosslinkers, are thought to promote contractility. Here, we examined how the abundance of motor and non-motor crosslinkers controls the speed of cytokinetic furrowing. We built a minimal model to simulate the contractile dynamics of the C. elegans zygote cytokinetic ring. This model predicted that intermediate levels of non-motor crosslinkers would allow maximal contraction speed, which we found to be the case for the scaffold protein anillin, in vivo. Our model also demonstrated a non-linear relationship between the abundance of motor ensembles and contraction speed. In vivo, thorough depletion of non-muscle myosin II delayed furrow initiation, slowed F-actin alignment, and reduced maximum contraction speed, but partial depletion allowed faster-than-expected kinetics. Thus, both motor and non-motor crosslinkers promote cytokinetic ring closure when present at low levels, but act as a brake when present at higher levels. Together, our findings extend the growing appreciation for the roles of crosslinkers, but reveal that they not only drive but also brake cytoskeletal remodeling.

Anillin propels myosin-independent constriction of actin rings

“…Theoretical work and in vivo experiments suggest that possible sources of the driving force underlying myosin-independent constriction mechanisms depend on actin-crosslinking proteins and actin filament disassembly (16)(17)(18)(19)(20). In microtubule networks, similar force-generating mechanisms, independent of molecular motors, are directly experimentally observed.…”

Regulation and Assembly of Actomyosin Contractile Rings in Cytokinesis and Cell Repair

“…Anillin also links RhoA to actin, myosin, or centralspindlin complexes to the cortex, thereby stabilizing regulatory and structural elements (discussed in section “Cell shape, tension, and MT‐independent control of cytokinetic rings”). In Drosophila , anillin is also required to coordinate the transition to midbody ring formation (Kechad et al, ), and work on C. elegans cytokinesis shows that contraction speed is maximized in the presence of moderate levels of anillin (Descovich et al, ). In the budding yeast Candida albicans ( Candida ), interaction of the anillin‐related protein integrin‐like protein 1 (Int1) with septin Sep7 may also help maintain genome stability and ploidy by preventing diffusion of Lte1 (Orellana‐Munoz et al, ).…”

“…In S. pombe cytokinesis, dynamic actin bundling by intermediate levels of the alpha‐actinin Ain1 is important for filament organization, as cells with less dynamic alpha‐actinins show delayed ring formation and inhibited ring contraction (Li et al, ). Work on C. elegans cytokinesis also shows that contraction speed is maximized at moderate levels of crosslinkers (Descovich et al, ). In mammalian cytokinesis, the Ca 2+ ‐sensing ability of alpha‐actinin is important for actin accumulation at the equator during early furrow initiation, but normal RhoA localization is retained in alpha‐actinin‐deficient cells, which ultimately are able to successfully complete cytokinesis (Jayadev et al, ).…”