Anthrax toxin receptor 2a controls mitotic spindle positioning

Nat Cell Biol. 2013 Jan;15(1):28-39. doi: 10.1038/ncb2632. Epub 2012 Dec 2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Bacterial Proteins / biosynthesis
  • Bacterial Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Membrane / metabolism
  • Cell Polarity
  • Cytoskeleton / metabolism
  • Doublecortin Domain Proteins
  • Embryo, Nonmammalian / cytology
  • Formins
  • Gene Knockdown Techniques
  • Germ Layers / cytology
  • Germ Layers / metabolism
  • Luminescent Proteins / biosynthesis
  • Luminescent Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Mitosis
  • Monomeric GTP-Binding Proteins / metabolism
  • Monomeric GTP-Binding Proteins / physiology
  • Morpholinos / genetics
  • Neuropeptides / metabolism
  • Protein Transport
  • Receptors, Peptide / genetics
  • Receptors, Peptide / metabolism
  • Receptors, Peptide / physiology*
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Fusion Proteins / genetics
  • Spindle Apparatus / metabolism*
  • Time-Lapse Imaging
  • Wnt Signaling Pathway
  • Zebrafish
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism
  • Zebrafish Proteins / physiology*
  • rho-Associated Kinases / metabolism

Substances

  • Actins
  • Antxr2a protein, zebrafish
  • Bacterial Proteins
  • Carrier Proteins
  • Doublecortin Domain Proteins
  • Formins
  • Luminescent Proteins
  • Microtubule-Associated Proteins
  • Morpholinos
  • Neuropeptides
  • Receptors, Peptide
  • Recombinant Fusion Proteins
  • Zebrafish Proteins
  • diaph2 protein, zebrafish
  • yellow fluorescent protein, Bacteria
  • Rock2a protein, zebrafish
  • rho-Associated Kinases
  • Monomeric GTP-Binding Proteins
  • rhoab protein, zebrafish