Spire and Formin 2 synergize and antagonize in regulating actin assembly in meiosis by a ping-pong mechanism

Pierre Montaville, Antoine Jégou, Julien Pernier, Christel Compper, Bérengère Guichard, Binyam Mogessie, Melina Schuh, Guillaume Romet-Lemonne, Marie-France Carlier

Research output: Contribution to journalArticle (Academic Journal)peer-review

52 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)e1001795
JournalPLoS Biology
Volume12
Issue number2
DOIs
Publication statusPublished - Feb 2014

Keywords

  • Actins
  • Animals
  • Cells, Cultured
  • Feedback, Physiological
  • Humans
  • Kinetics
  • Meiosis
  • Mice
  • Microfilament Proteins
  • Nuclear Proteins
  • Oocytes
  • Profilins
  • Protein Binding
  • Protein Multimerization
  • Journal Article
  • Research Support, Non-U.S. Gov't

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