PLK1 plays dual roles in centralspindlin regulation during cytokinesis

J Cell Biol. 2019 Apr 1;218(4):1250-1264. doi: 10.1083/jcb.201805036. Epub 2019 Feb 6.

Abstract

Cytokinesis begins upon anaphase onset. An early step involves local activation of the small GTPase RhoA, which triggers assembly of an actomyosin-based contractile ring at the equatorial cortex. Here, we delineated the contributions of PLK1 and Aurora B to RhoA activation and cytokinesis initiation in human cells. Knock-down of PRC1, which disrupts the spindle midzone, revealed the existence of two pathways that can initiate cleavage furrow ingression. One pathway depends on a well-organized spindle midzone and PLK1, while the other depends on Aurora B activity and centralspindlin at the equatorial cortex and can operate independently of PLK1. We further show that PLK1 inhibition sequesters centralspindlin onto the spindle midzone, making it unavailable for Aurora B at the equatorial cortex. We propose that PLK1 activity promotes the release of centralspindlin from the spindle midzone through inhibition of PRC1, allowing centralspindlin to function as a regulator of spindle midzone formation and as an activator of RhoA at the equatorial cortex.

Publication types

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

MeSH terms

  • Animals
  • Aurora Kinase B / genetics
  • Aurora Kinase B / metabolism
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cytokinesis*
  • Enzyme Activation
  • HeLa Cells
  • Humans
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism*
  • Microtubules / enzymology*
  • Microtubules / genetics
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Polo-Like Kinase 1
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Protein Transport
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Signal Transduction
  • Spindle Apparatus / enzymology*
  • Spindle Apparatus / genetics
  • rhoA GTP-Binding Protein / genetics
  • rhoA GTP-Binding Protein / metabolism

Substances

  • Aurora Kinase B
  • Caenorhabditis elegans Proteins
  • Cell Cycle Proteins
  • Microtubule-Associated Proteins
  • Phosphoproteins
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins
  • rhoA GTP-Binding Protein
  • Polo-Like Kinase 1
  • CYK-4 protein, C elegans
  • PRC1 protein, human
  • SPD-1 protein, C elegans
  • spindlin
  • RHOA protein, human
  • AURKB protein, human