TY - JOUR TI - Profilin and formin constitute a pacemaker system for robust actin filament growth AU - Funk, Johanna AU - Merino, Felipe AU - Venkova, Larisa AU - Heydenreich, Lina AU - Kierfeld, Jan AU - Vargas, Pablo AU - Raunser, Stefan AU - Piel, Matthieu AU - Bieling, Peter A2 - Lappalainen, Pekka A2 - Akhmanova, Anna A2 - Lappalainen, Pekka VL - 8 PY - 2019 DA - 2019/10/24 SP - e50963 C1 - eLife 2019;8:e50963 DO - 10.7554/eLife.50963 UR - https://doi.org/10.7554/eLife.50963 AB - 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. KW - cytokeleton KW - actin KW - polymerization KW - polymerase KW - profilin KW - formin JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -