PAR-4 and anillin regulate myosin to coordinate spindle and furrow position during asymmetric division

J Cell Biol. 2015 Sep 28;210(7):1085-99. doi: 10.1083/jcb.201503006.

Abstract

During asymmetric cell division, the mitotic spindle and polarized myosin can both determine the position of the cytokinetic furrow. However, how cells coordinate signals from the spindle and myosin to ensure that cleavage occurs through the spindle midzone is unknown. Here, we identify a novel pathway that is essential to inhibit myosin and coordinate furrow and spindle positions during asymmetric division. In Caenorhabditis elegans one-cell embryos, myosin localizes at the anterior cortex whereas the mitotic spindle localizes toward the posterior. We find that PAR-4/LKB1 impinges on myosin via two pathways, an anillin-dependent pathway that also responds to the cullin CUL-5 and an anillin-independent pathway involving the kinase PIG-1/MELK. In the absence of both PIG-1/MELK and the anillin ANI-1, myosin accumulates at the anterior cortex and induces a strong displacement of the furrow toward the anterior, which can lead to DNA segregation defects. Regulation of asymmetrically localized myosin is thus critical to ensure that furrow and spindle midzone positions coincide throughout cytokinesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / cytology
  • Caenorhabditis elegans / embryology*
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Cytokinesis / physiology*
  • Myosins / genetics
  • Myosins / metabolism*
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Spindle Apparatus / genetics
  • Spindle Apparatus / metabolism*
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism

Substances

  • Caenorhabditis elegans Proteins
  • Zebrafish Proteins
  • Melk protein, zebrafish
  • PAR-3 protein, C elegans
  • PIG-1 protein, C elegans
  • Protein Serine-Threonine Kinases
  • Myosins