May 2018: How Formins Respond to Biochemical and Mechanical Conditions
It is now well established that formins are central players in the regulation of the dynamics of almost all actin networks in cells. But how their activities are modulated by biochemistry and mechanics is far less well understood. Researchers from the ‘Regulation of Actin Assembly Dynamics’ team of the Institut Jacques Monod have studied in vitro actin filament elongation induced by mDia1 and mDia2 mammalian formins. This work, published in eLife, has shown that filament length can be increased by the presence of profilin, a protein that forms binary complexes with actin, but is highly diminished if a pulling force is applied between formins and actin filaments. How cells limit formin dissociation under tension is now a key question for future studies.
Hundreds of proteins regulate actin assembly in cells, but formins have the unique capability to processively track the barbed ends of actin filaments while promoting their rapid elongation. In mammals, mDia1 and mDia2 are key formins regulating the actin cortex and motile networks. Single filament microscopy assays has revealed that formin processivity, i.e. for how long formins remain bound to barbed ends, was decreased when formins are elongating filaments faster. However, for a defined elongation rate, formin processivity was improved when more profilin was present, which increased the frequency of contacts between one formin sub-domain and the barbed end of the actin filament. Applying a pulling force on formins strongly decreased its processivity, independently of profilin. These results, confronted to a theoretical model, indicate that formins can detach from filament barbed ends following two different routes.
- For more information:
Cao, L., Kerleau, M., Suzuki, E.L., Wioland, H., Jouet, S., Guichard, B., Lenz, M., Romet-Lemonne, G., and Jégou, A. (2018).
Modulation of formin processivity by profilin and mechanical tension.
eLife Sciences 7, e34176.
Contact : Antoine Jégou, team : “Regulation of Actin Assembly Dynamics”