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.

journal_name

PLoS Biol

journal_title

PLoS biology

authors

Montaville P,Jégou A,Pernier J,Compper C,Guichard B,Mogessie B,Schuh M,Romet-Lemonne G,Carlier MF

doi

10.1371/journal.pbio.1001795

subject

Has Abstract

pub_date

2014-02-25 00:00:00

pages

e1001795

issue

2

eissn

1544-9173

issn

1545-7885

pii

PBIOLOGY-D-13-03073

journal_volume

12

pub_type

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