Modulating Formin Processivity with Mechanical and Biochemical Factors

Abstract

In cells, actin filament assembly is regulated by actin regulatory proteins and mechanical context. Formin proteins are able to track a growing filament barbed end and dramatically enhance its elongation from profilin-actin. They can do so while being anchored to a surface, thereby allowing the transmission of mechanical tension while the filament keeps on elongating. We have recently shown that tension applied to the filament accelerates its elongation and that, in the absence of actin monomers, formins were able to track depolymerizing filaments in spite of an opposing tension of a few picoNewtons (Jegou et al., Nat. Commun. 2013). Here, with similar single filament experiments using microfluidics, we investigate the impact of tension and protein concentration on another key feature of formins, processivity. We show that tension drastically enhances the detachment of the formin from the filament barbed end, both in the elongation and the depolymerization regime. Moreover, we find that tension and Capping Protein act in synergy to rapidly detach the filament from the formin. We also characterize the impact of actin and profilin concentrations on formin processivity.