title: Spire-type actin nucleators cooperate with Formin-2 to drive asymmetric oocyte division.
abstract: 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 [1], 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 [2-6]. 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.
authors.affiliation: Medical Research Council, Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom.
authors.forename: Sybille
authors.initials: S
authors.lastname: Pfender
authors.forename: Vitaliy
authors.initials: V
authors.lastname: Kuznetsov
authors.forename: Sandra
authors.initials: S
authors.lastname: Pleiser
authors.forename: Eugen
authors.initials: E
authors.lastname: Kerkhoff
authors.forename: Melina
authors.initials: M
authors.lastname: Schuh
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002455:Cell Division / Q000235:genetics / Q000502:physiology*; D016764:Cell Polarity; D000080865:Formins; D051379:Mice; D008840:Microfilament Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D009687:Nuclear Proteins / Q000378:metabolism / Q000502:physiology*; D009865:Oocytes / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D034622:RNA Interference; D008941:Spindle Apparatus / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D000199:Actins; D000080865:Formins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C556674:Spir-2 protein, mouse; C493004:Spire1 protein, mouse; C549436:formin 2 protein, mouse