Goryachev AB et al. (2016), How to make a static cytokinetic furrow out of ...

ECB-ART-44622

Small GTPases 2016 Apr 02;72:65-70. doi: 10.1080/21541248.2016.1168505.

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How to make a static cytokinetic furrow out of traveling excitable waves.

Goryachev AB , Leda M , Miller AL , von Dassow G , Bement WM .

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Emergence of the cytokinetic Rho zone that orchestrates formation and ingression of the cleavage furrow had been explained previously via microtubule-dependent cortical concentration of Ect2, a guanine nucleotide exchange factor for Rho. The results of a recent publication now demonstrate that, en route from resting cortex to fully established furrow, there lies a regime of cortical excitability in which Rho activity and F-actin play the roles of the prototypical activator and inhibitor, respectively. This cortical excitability is manifest as dramatic traveling waves on the cortex of oocytes and embryos of frogs and starfish. These waves are initiated by autocatalytic activation of Rho at the wave front and extinguished by F-actin-dependent inhibition at their back. It is still unclear how propagating excitable Rho-actin waves give rise to the stable co-existence of Rho activity and F-actin density in the static cleavage furrow during cytokinesis. It is possible that some central spindle-associated signaling molecule simply turns off the inhibition of Rho activity by F-actin. However, mathematical modeling suggests a distinct scenario in which local "re-wiring" of the Rho-actin coupling in the furrow is no longer necessary. Instead, the model predicts that the continuously rising level of Ect2 produces in the furrow a qualitatively new stable steady state that replaces excitability and brings about the stable co-existence of high Rho activity and dense F-actin despite the continuing inhibition of Rho by F-actin.

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Genes referenced: ect2 LOC100893746 LOC115919910 LOC590297

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	Figure 1. Spatial profiles of the Rho activity and F-actin accumulation are distinct in a traveling wave and a static structure. (A) Relationships between the prototypical activator and inhibitor shown here schematically can generate both waves of excitable dynamics and static structures. (B) In a schematic wave spatial profile, the activator (Rho) always precedes the inhibitor (F-actin). (C) In an immobile structure, such as the cytokinetic furrow or Turing pattern, the activator and inhibitor peak together. The maxima of Rho and F-actin are scaled to be equal. The direction of wave propagation in (B) is shown by the arrow.
	Figure 2. Scheme of the biochemical reactions described by the mathematical model of excitable Rho dynamics (adapted from Ref. 21). Inactive Rho (green rectangles) shuttles between the membrane and the cytoplasm and becomes converted into the active form (red rectangle) by Ect2. Active Rho promotes actin polymerization that, in turn, facilitates Rho inactivation, possibly, by recruiting a Rho GAP. In the absence of Rho activity, F-actin depolymerizes and recycles back into the cytoplasm.
	Figure 3. Mathematical model predicts that the type of cortical dynamics observed in dividing cells is determined by the local concentration of the Rho GEF Ect2. Cortical loci positioned along the division axis of a cell (upper row) are differentiated by the local concentration of Ect2 that increases toward the cell equator and exhibit distinct types of the local Rho-actin dynamics schematically shown by the characteristic phase portraits (bottom row). (A) Weak excitability far from the nascent furrow. (B) Well-developed excitable waves in the vicinity of the furrow. (C) High Rho activity and F-actin accumulation stably co-exist in the furrow where a new stable steady-state emerges due to the high local concentration of Ect2. Local concentration of Ect2 at the cortical loci indicated by filled black circles is shown schematically by the intensity of green shading (upper row). Shown on the phase portraits (bottom row): red curves – the activator nullclines; black curves – the inhibitor nullclines; magenta curves – excitable trajectories; orange arrows – initial perturbations required to induce excitable response; blue filled circles – the resting cortical steady state; red filled circle – the high activity cortical steady-state in the furrow; black open circle – the unstable steady state. See text for discussion.

References [+] :

Allard, Traveling waves in actin dynamics and cell motility. 2013, Pubmed