The role of PLK1-phosphorylated SVIL in myosin II activation and cytokinetic furrowing

J Cell Sci. 2013 Aug 15;126(Pt 16):3627-37. doi: 10.1242/jcs.124818. Epub 2013 Jun 7.

Abstract

Polo-like kinase 1 (PLK1) is a widely conserved serine/threonine kinase that regulates progression of multiple stages of mitosis. Although extensive studies about PLK1 functions during cell division have been performed, it is still not known how PLK1 regulates myosin II activation at the equatorial cortex and ingression of the cleavage furrow. In this report, we show that an actin/myosin-II-binding protein, supervillin (SVIL), is a substrate of PLK1. PLK1 phosphorylates Ser238 of SVIL, which can promote the localization of SVIL to the central spindle and association with PRC1. Expression of a PLK1 phosphorylation site mutant, S238A-SVIL, inhibited myosin II activation at the equatorial cortex and induced aberrant furrowing. SVIL has both actin- and myosin-II-binding regions in the N-terminus. Expression of ΔMyo-SVIL (deleted of the myosin-II-binding region), but not of ΔAct-SVIL (deleted of actin-binding region), reduced myosin II activation and caused defects in furrowing. Our study indicates a possible role of phosphorylated SVIL as a molecular link between the central spindle and the contractile ring to coordinate the activation of myosin II for the ingression of the cleavage furrow.

Keywords: Central spindle; Cytokinesis; PLK1; Phosphorylation; SVIL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cytokinesis / physiology
  • HeLa Cells
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism*
  • Myosin Type II / genetics
  • Myosin Type II / metabolism*
  • Phosphorylation
  • Polo-Like Kinase 1
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Spindle Apparatus / metabolism*
  • Transfection

Substances

  • Cell Cycle Proteins
  • Membrane Proteins
  • Microfilament Proteins
  • Proto-Oncogene Proteins
  • SVIL protein, human
  • Protein Serine-Threonine Kinases
  • Myosin Type II