Tension within the network could

Tension within the network could be explained by two potential mechanisms: the more classical contractility that is dependent on motor proteins that are pulling pregnane x receptor filaments towards each other [10]; or contractility that is caused by disassembly of a crosslinked network of actin filaments [2]. To test which scenario is more likely to be the source of force generation, Bun et al.[6] analyzed network contraction rates in response to different perturbations. Inhibition of non-muscle myosin II, the motor protein that is typically involved in generating contractile force in actin networks [11,12], did not affect the rate of network contraction [6]. Similarly, no effect was observed after inhibition of myosin Vb [6], the myosin that drives the dynamics of the actin network in mouse oocytes that is required for vesicle transport as well as spindle and nuclear positioning 13, 14, 15. Moreover, motor-dependent contraction should over time lead to a massive increase in network density; however, such an increase was not observed in vivo, pointing instead towards a disassembly-dependent contraction mechanism [6]. Simulations of a disassembly-based contraction mechanism predicted that stabilization of actin filaments should lead to slower contraction rates, whereas destabilization of actin filaments should accelerate contraction [6]. To test these predictions, Bun et al.[6] injected into oocytes varying amounts of the calponin homology domain of utrophin [16], which stabilizes actin filaments at high doses [14]. In support of a disassembly-dependent mechanism, they observed that the rate of contraction decreased upon stabilization of the actin filaments. Strikingly, treatment of oocytes with low doses of latrunculin A, which destabilizes actin filaments, caused a dramatic increase in contraction rates. Together, these results were consistent with the model that network contraction is driven by disassembly of actin filaments. For actin disassembly to cause network contraction, a coupling factor is required to harness the free energy of filament disassembly for network contraction [2]. Such a factor could be a molecule that is able to track the depolymerizing end of one filament, while at the same time being connected to an adjacent filament (Figure 1B). Based on previous publications, formins could perform this function [5,17, 18, 19]. Indeed, the authors [6] found that the contraction of the network was significantly compromised when they treated oocytes with the formin inhibitor SMIFH2. However, the specific formin that might be involved in contraction remains to be identified. What is the advantage of disassembly-driven contraction over motor-protein-driven contraction? The authors [6] argue that, if motor proteins were the driving force of chromosome transport in starfish oocytes, the density of the actin network would gradually increase during contraction. This in turn would lead to the formation of a very dense actin network around the chromosomes by the end of chromosome congression. This dense actin network could potentially hinder the formation of the first meiotic spindle by shielding the chromosomes from microtubules, making the capture of chromosomes by microtubules inefficient. The disassembly-driven mechanism leads to the complete disassembly of the actin network by the end of chromosome congression, clearing the path for establishing microtubule–chromosome interactions. Bun et al.[6] have established a powerful in vivo model for studying the mechanism of disassembly-driven actin network contraction. In the future, it will be interesting to identify the molecular players that are involved in the formation of the network and its contraction, including the coupling factor that harnesses the free energy of actin disassembly. Identifying the minimal set of components that is needed to produce contraction would enable reconstitution of disassembly-driven contractile systems in vitro. This would allow a much more detailed investigation of this as yet poorly understood mechanism of actin network contraction.