title: Spire and Formin 2 synergize and antagonize in regulating actin assembly in meiosis by a ping-pong mechanism.
abstract: In mammalian oocytes, three actin binding proteins, Formin 2 (Fmn2), Spire, and profilin, synergistically organize a dynamic cytoplasmic actin meshwork that mediates translocation of the spindle toward the cortex and is required for successful fertilization. Here we characterize Fmn2 and elucidate the molecular mechanism for this synergy, using bulk solution and individual filament kinetic measurements of actin assembly dynamics. We show that by capping filament barbed ends, Spire recruits Fmn2 and facilitates its association with barbed ends, followed by rapid processive assembly and release of Spire. In the presence of actin, profilin, Spire, and Fmn2, filaments display alternating phases of rapid processive assembly and arrested growth, driven by a "ping-pong" mechanism, in which Spire and Fmn2 alternately kick off each other from the barbed ends. The results are validated by the effects of injection of Spire, Fmn2, and their interacting moieties in mouse oocytes. This original mechanism of regulation of a Rho-GTPase-independent formin, recruited by Spire at Rab11a-positive vesicles, supports a model for modulation of a dynamic actin-vesicle meshwork in the oocyte at the origin of asymmetric positioning of the meiotic spindle.
authors.affiliation: Laboratoire d'Enzymologie et Biochimie Structurale, CNRS, Gif-sur-Yvette, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Montaville
authors.affiliation: Laboratoire d'Enzymologie et Biochimie Structurale, CNRS, Gif-sur-Yvette, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Jégou
authors.affiliation: Laboratoire d'Enzymologie et Biochimie Structurale, CNRS, Gif-sur-Yvette, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Pernier
authors.affiliation: Laboratoire d'Enzymologie et Biochimie Structurale, CNRS, Gif-sur-Yvette, France.
authors.forename: Christel
authors.initials: C
authors.lastname: Compper
authors.affiliation: Laboratoire d'Enzymologie et Biochimie Structurale, CNRS, Gif-sur-Yvette, France.
authors.forename: Bérengère
authors.initials: B
authors.lastname: Guichard
authors.affiliation: MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.
authors.forename: Binyam
authors.initials: B
authors.lastname: Mogessie
authors.affiliation: MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.
authors.forename: Melina
authors.initials: M
authors.lastname: Schuh
authors.affiliation: Laboratoire d'Enzymologie et Biochimie Structurale, CNRS, Gif-sur-Yvette, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Romet-Lemonne
authors.affiliation: Laboratoire d'Enzymologie et Biochimie Structurale, CNRS, Gif-sur-Yvette, France.
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Carlier
mesh_terms: D000199:Actins / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D025461:Feedback, Physiological; D000080865:Formins; D006801:Humans; D007700:Kinetics; D008540:Meiosis; D051379:Mice; D008840:Microfilament Proteins / Q000737:chemistry / Q000502:physiology*; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins / Q000737:chemistry / Q000502:physiology*; D009865:Oocytes / Q000378:metabolism; D051304:Profilins / Q000737:chemistry; D011485:Protein Binding; D055503:Protein Multimerization
chemical_list: D000199:Actins; D000080865:Formins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D051304:Profilins; C000592292:SPIRE1 protein, human; C549436:formin 2 protein, mouse