Spire-Type Actin Nucleators Cooperate with Formin-2 to Drive Asymmetric Oocyte Division

Oocytes mature into eggs by extruding half of their chromosomes in a small cell termed the polar body. Asymmetric oocyte division is essential for fertility 1Leader B. Lim H. Carabatsos M.J. Harrington A. Ecsedy J. Pellman D. Maas R. Leder P. Formin-2, polyploidy, hypofertility and positioning of the meiotic spindle in mouse oocytes.Nat. Cell Biol. 2002; 4: 921-928Crossref PubMed Scopus (269) Google Scholar, but despite its importance, little is known about its mechanism. In mammals, the meiotic spindle initially forms close to the center of the oocyte. Thus, two steps are required for asymmetric meiotic division: first, asymmetric spindle positioning and second, polar body extrusion. Here, we identify Spire1 and Spire2 as new key factors in asymmetric division of mouse oocytes. Spire proteins are novel types of actin nucleators that drive nucleation of actin filaments with their four WH2 actin-binding domains 2Quinlan M.E. Heuser J.E. Kerkhoff E. Mullins R.D. Drosophila Spire is an actin nucleation factor.Nature. 2005; 433: 382-388Crossref PubMed Scopus (258) Google Scholar, 3Ducka A.M. Joel P. Popowicz G.M. Trybus K.M. Schleicher M. Noegel A.A. Huber R. Holak T.A. Sitar T. Structures of actin-bound Wiskott-Aldrich syndrome protein homology 2 (WH2) domains of Spire and the implication for filament nucleation.Proc. Natl. Acad. Sci. USA. 2010; 107: 11757-11762Crossref PubMed Scopus (29) Google Scholar, 4Rebowski G. Boczkowska M. Hayes D.B. Guo L. Irving T.C. Dominguez R. X-ray scattering study of actin polymerization nuclei assembled by tandem W domains.Proc. Natl. Acad. Sci. USA. 2008; 105: 10785-10790Crossref PubMed Scopus (32) Google Scholar, 5Dahlgaard K. Raposo A.A. Niccoli T. St Johnston D. Capu and Spire assemble a cytoplasmic actin mesh that maintains microtubule organization in the Drosophila oocyte.Dev. Cell. 2007; 13: 539-553Abstract Full Text Full Text PDF PubMed Scopus (122) Google Scholar, 6Bosch M. Le K.H. Bugyi B. Correia J.J. Renault L. Carlier M.F. Analysis of the function of Spire in actin assembly and its synergy with formin and profilin.Mol. Cell. 2007; 28: 555-568Abstract Full Text Full Text PDF PubMed Scopus (87) Google Scholar. We show that Spire1 and Spire2 first mediate asymmetric spindle positioning by assembling an actin network that serves as a substrate for spindle movement. Second, they drive polar body extrusion by promoting assembly of the cleavage furrow. Our data suggest that Spire1 and Spire2 cooperate with Formin-2 (Fmn2) to nucleate actin filaments in mouse oocytes and that both types of nucleators act as a functional unit. This study not only reveals how Spire1 and Spire2 drive two critical steps of asymmetric oocyte division, but it also uncovers the first physiological function of Spire-type actin nucleators in vertebrates.