title: Anthrax toxin receptor 2a controls mitotic spindle positioning.
abstract: Oriented mitosis is essential during tissue morphogenesis. The Wnt/planar cell polarity (Wnt/PCP) pathway orients mitosis in a number of developmental systems, including dorsal epiblast cell divisions along the animal-vegetal (A-V) axis during zebrafish gastrulation. How Wnt signalling orients the mitotic plane is, however, unknown. Here we show that, in dorsal epiblast cells, anthrax toxin receptor 2a (Antxr2a) accumulates in a polarized cortical cap, which is aligned with the embryonic A-V axis and forecasts the division plane. Filamentous actin (F-actin) also forms an A-V polarized cap, which depends on Wnt/PCP and its effectors RhoA and Rock2. Antxr2a is recruited to the cap by interacting with actin. Antxr2a also interacts with RhoA and together they activate the diaphanous-related formin zDia2. Mechanistically, Antxr2a functions as a Wnt-dependent polarized determinant, which, through the action of RhoA and zDia2, exerts torque on the spindle to align it with the A-V axis.
authors.affiliation: Departments of Biochemistry and Molecular Biology, Sciences II, 30 Quai Ernest-Ansermet, CH-1211 Geneva 4, Switzerland.
authors.forename: I
authors.initials: I
authors.lastname: Castanon
authors.forename: L
authors.initials: L
authors.lastname: Abrami
authors.forename: L
authors.initials: L
authors.lastname: Holtzer
authors.forename: C P
authors.initials: CP
authors.lastname: Heisenberg
authors.forename: F G
authors.initials: FG
authors.lastname: van der Goot
authors.forename: M
authors.initials: M
authors.lastname: González-Gaitán
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics; D002352:Carrier Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D016764:Cell Polarity; D003599:Cytoskeleton / Q000378:metabolism; D000089622:Doublecortin Domain Proteins; D004625:Embryo, Nonmammalian / Q000166:cytology; D000080865:Formins; D055785:Gene Knockdown Techniques; D005855:Germ Layers / Q000166:cytology / Q000378:metabolism; D008164:Luminescent Proteins / Q000096:biosynthesis / Q000235:genetics; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008938:Mitosis; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism / Q000502:physiology; D060172:Morpholinos / Q000235:genetics; D009479:Neuropeptides / Q000378:metabolism; D021381:Protein Transport; D018000:Receptors, Peptide / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D008941:Spindle Apparatus / Q000378:metabolism*; D059008:Time-Lapse Imaging; D060449:Wnt Signaling Pathway; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D000199:Actins; C578377:Antxr2a protein, zebrafish; D001426:Bacterial Proteins; D002352:Carrier Proteins; D000089622:Doublecortin Domain Proteins; D000080865:Formins; D008164:Luminescent Proteins; D008869:Microtubule-Associated Proteins; D060172:Morpholinos; D009479:Neuropeptides; D018000:Receptors, Peptide; D011993:Recombinant Fusion Proteins; D029961:Zebrafish Proteins; C534034:diaph2 protein, zebrafish; C054562:yellow fluorescent protein, Bacteria; C577492:Rock2a protein, zebrafish; D054460:rho-Associated Kinases; D020559:Monomeric GTP-Binding Proteins; C549425:rhoab protein, zebrafish