How does cofilin regulate actomyosin formation and Myosin II mediated contractility?2018-02-06T11:09:25+00:00

How does cofilin regulate actomyosin formation and Myosin II mediated contractility?

Along with actin filament disassembly or severing, ADF/cofilin was recently shown to carry out another important role; specifically the regulation of Myosin II mediated contractility and actomyosin formation. This was proposed to result from competitive antagonism, where myosin II must compete with cofilin for binding sites on F-actin [1].

In this study it was shown that the binding affinities of each protein are ATP dependent, with ADF/cofilin possessing a competitive advantage at cellular levels of ATP, whilst in the absence of ATP the binding affinities of each protein is similar. Importantly, a reduction in the levels of both ADF and cofilin lead to an increase in the concentration of F-actin, a finding that was attributed not to a loss in cofilin mediated F-actin severing, but rather to an increase in myosin-II dependent actin assembly via its crosslinking properties. This was confirmed with the introduction of blebbistatin which inhibited myosin II activity and subsequently lead to the disassembly of F-actin [1].

The implications for this role of ADF/cofilin may be described at the molecular level, however as shown by Wiggan O et al the consequences are clearly evident at a cellular level, with persistent membrane blebs being observed in HeLa cells depleted of the proteins [1]. As it had previously been reported that non-apoptotic blebs were produced as a means of releasing cell tension, it is probable that the observed phenotype occurred for a similar purpose, and highlights the importance of ADF/cofilin in the regulation of cortical tension and actomyosin activity [1].

Despite these findings, in some situations a cooperative relationship between ADF/cofilin and Myosin-II appears to exist. This has been described, for example, in a study investigating actomyosin ring constriction in budding yeast cells [2]. Supporting earlier findings [3][4], this study also confirmed that deletion or inhibition of the motor-domain of Myosin II (MyoI) did not completely prevent constriction, but noted that a 40% reduction in the rate of contraction was observed. This was in contrast to mutations in cofilin, or stabilization of actin filaments, which did prevent actomyosin ring constriction. Model simulations using this data indicated a role of Myosin-II in the promotion of cofilin mediated depolymerization, and it was suggested that it is the disassembly of F-actin that is the primary contributor to actomyosin ring constriction [2].

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  1. Wiggan O, Shaw AE, DeLuca JG, and Bamburg JR. ADF/cofilin regulates actomyosin assembly through competitive inhibition of myosin II binding to F-actin. Dev. Cell 2012; 22(3):530-43. [PMID: 22421043]
  2. Mendes Pinto I, Rubinstein B, Kucharavy A, Unruh JR, and Li R. Actin depolymerization drives actomyosin ring contraction during budding yeast cytokinesis. Dev. Cell 2012; 22(6):1247-60. [PMID: 22698284]
  3. Fang X, Luo J, Nishihama R, Wloka C, Dravis C, Travaglia M, Iwase M, Vallen EA, and Bi E. Biphasic targeting and cleavage furrow ingression directed by the tail of a myosin II. J. Cell Biol. 2010; 191(7):1333-50. [PMID: 21173112]
  4. Lord M, Laves E, and Pollard TD. Cytokinesis depends on the motor domains of myosin-II in fission yeast but not in budding yeast. Mol. Biol. Cell 2005; 16(11):5346-55. [PMID: 16148042]