Abstract
The actin cytoskeleton drives many essential biological processes, from cell morphogenesis to motility. Assembly of functional actin networks requires control over the speed at which actin filaments grow. How this can be achieved at the high and variable levels of soluble actin subunits found in cells is unclear. Here we reconstitute assembly of mammalian, non-muscle actin filaments from physiological concentrations of profilin-actin. We discover that under these conditions, filament growth is limited by profilin dissociating from the filament end and the speed of elongation becomes insensitive to the concentration of soluble subunits. Profilin release can be directly promoted by formin actin polymerases even at saturating profilin-actin concentrations. We demonstrate that mammalian cells indeed operate at the limit to actin filament growth imposed by profilin and formins. Our results reveal how synergy between profilin and formins generates robust filament growth rates that are resilient to changes in the soluble subunit concentration.
Highlights
Eukaryotic cells move, change their shape and organize their interior through dynamic actin networks
We estimated the profilin-actin concentration around 50–200 mM, depending on mammalian cell type (Figure 1D–E, see Materials and methods section for details concerning the estimation of soluble profilin-actin levels)
Contrary to the textbook model, we demonstrate that actin filament elongation under physiological conditions is not limited by the diffusional encounter between soluble subunits and filament ends
Summary
Eukaryotic cells move, change their shape and organize their interior through dynamic actin networks. Profilin shields the barbed end side of actin monomers to suppress spontaneous nucleation (Schutt et al, 1993). The speed of filament elongation over a limited concentration range of profilin-actin fits a linear model for a binding-controlled reaction (Blanchoin and Pollard, 2002; Oosawa and Asakura, 1975). This has led to the idea that the concentration of soluble subunits is the central parameter that controls the speed of actin growth (Blanchoin et al, 2014; Carlier and Shekhar, 2017; Pollard et al, 2000). Actin elongation has only been studied at low, non-physiological levels of soluble subunits until now
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