title: Profilin Interaction with Actin Filament Barbed End Controls Dynamic Instability, Capping, Branching, and Motility.
abstract: Cell motility and actin homeostasis depend on the control of polarized growth of actin filaments. Profilin, an abundant regulator of actin dynamics, supports filament assembly at barbed ends by binding G-actin. Here, we demonstrate how, by binding and destabilizing filament barbed ends at physiological concentrations, profilin also controls motility, cell migration, and actin homeostasis. Profilin enhances filament length fluctuations. Profilin competes with Capping Protein at barbed ends, which generates a lower amount of profilin-actin than expected if barbed ends were tightly capped. Profilin competes with barbed end polymerases, such as formins and VopF, and inhibits filament branching by WASP-Arp2/3 complex by competition for filament barbed ends, accounting for its as-yet-unknown effects on motility and metastatic cell migration observed in this concentration range. In conclusion, profilin is a major coordinator of polarized growth of actin filaments, controlled by competition between barbed end cappers, trackers, destabilizers, and filament branching machineries.
authors.affiliation: Cytoskeleton Dynamics and Motility Group, I2BC, CNRS, Gif-sur-Yvette 91198, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Pernier
authors.affiliation: Cytoskeleton Dynamics and Motility Group, I2BC, CNRS, Gif-sur-Yvette 91198, France.
authors.forename: Shashank
authors.initials: S
authors.lastname: Shekhar
authors.affiliation: Cytoskeleton Dynamics and Motility Group, I2BC, CNRS, Gif-sur-Yvette 91198, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Jegou
authors.affiliation: Cytoskeleton Dynamics and Motility Group, I2BC, CNRS, Gif-sur-Yvette 91198, France.
authors.forename: Bérengère
authors.initials: B
authors.lastname: Guichard
authors.affiliation: Cytoskeleton Dynamics and Motility Group, I2BC, CNRS, Gif-sur-Yvette 91198, France. Electronic address: marie-france.carlier@i2bc.paris-saclay.fr.
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Carlier
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D000818:Animals; D002465:Cell Movement / Q000502:physiology; D003599:Cytoskeleton / Q000378:metabolism*; D051304:Profilins / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D011817:Rabbits
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D000199:Actins; D051304:Profilins
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