Formin and capping protein together embrace the actin filament in a ménage à trois

• Published in: Nature communications Vol. 6; no. 1; p. 8730
• Main Authors: Shekhar, Shashank, Kerleau, Mikael, Kühn, Sonja, Pernier, Julien, Romet-Lemonne, Guillaume, Jégou, Antoine, Carlier, Marie-France
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 13-11-2015; Nature Publishing Group; Nature Pub. Group
• Subjects: 631/45/535; 631/57/2272; 631/80/128/1276; 631/80/84/1757; 82; 82/62; Actin Capping Proteins - chemistry; Actin Capping Proteins - metabolism; Actin Cytoskeleton - chemistry; Actin Cytoskeleton - metabolism; Adaptor Proteins, Signal Transducing - chemistry; Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Animals; Electron microscopes; Humanities and Social Sciences; Humans; Kinetics; Life Sciences; Motility; multidisciplinary; Protein Binding; Proteins; Proteins - chemistry; Proteins - genetics; Proteins - metabolism; Rabbits; Science; Science (multidisciplinary); France
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms9730

Proteins targeting actin filament barbed ends play a pivotal role in motile processes. While formins enhance filament assembly, capping protein (CP) blocks polymerization. On their own, they both bind barbed ends with high affinity and very slow dissociation. Their barbed-end binding is thought to be mutually exclusive. CP has recently been shown to be present in filopodia and controls their morphology and dynamics. Here we explore how CP and formins may functionally coregulate filament barbed-end assembly. We show, using kinetic analysis of individual filaments by microfluidics-assisted fluorescence microscopy, that CP and mDia1 formin are able to simultaneously bind barbed ends. This is further confirmed using single-molecule imaging. Their mutually weakened binding enables rapid displacement of one by the other. We show that formin FMNL2 behaves similarly, thus suggesting that this is a general property of formins. Implications in filopodia regulation and barbed-end structural regulation are discussed.
Formins promote actin filament polymerization and capping protein blocks polymerization; both proteins are thought to exclude each other from barbed ends. Here the authors show that both proteins can simultaneously bind barbed ends in a ternary complex while enhancing each other's dissociation from the barbed end.