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PLoS Biol. 2014 Feb 25;12(2):e1001795. doi: 10.1371/journal.pbio.1001795. eCollection 2014 Feb.

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

Author information

1
Laboratoire d'Enzymologie et Biochimie Structurale, CNRS, Gif-sur-Yvette, France.
2
MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.

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.

PMID:
24586110
PMCID:
PMC3934834
DOI:
10.1371/journal.pbio.1001795
[Indexed for MEDLINE]
Free PMC Article

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