Dissecting temporal and spatial control of cytokinesis with a myosin II Inhibitor

Science. 2003 Mar 14;299(5613):1743-7. doi: 10.1126/science.1081412.

Abstract

Completion of cell division during cytokinesis requires temporally and spatially regulated communication from the microtubule cytoskeleton to the actin cytoskeleton and the cell membrane. We identified a specific inhibitor of nonmuscle myosin II, blebbistatin, that inhibited contraction of the cleavage furrow without disrupting mitosis or contractile ring assembly. Using blebbistatin and other drugs, we showed that exit from the cytokinetic phase of the cell cycle depends on ubiquitin-mediated proteolysis. Continuous signals from microtubules are required to maintain the position of the cleavage furrow, and these signals control the localization of myosin II independently of other furrow components.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anaphase
  • Aurora Kinases
  • Cell Division* / drug effects
  • Cell Movement / drug effects
  • Contractile Proteins / metabolism
  • Cyclin-Dependent Kinases / antagonists & inhibitors
  • Cyclin-Dependent Kinases / metabolism
  • DNA Replication
  • Enzyme Inhibitors / pharmacology
  • HeLa Cells
  • Heterocyclic Compounds, 4 or More Rings / chemistry
  • Heterocyclic Compounds, 4 or More Rings / isolation & purification
  • Heterocyclic Compounds, 4 or More Rings / pharmacology*
  • Humans
  • Kinesins / metabolism
  • Leupeptins / pharmacology
  • Microtubules / physiology
  • Mitosis / drug effects
  • Myosin Type II / antagonists & inhibitors*
  • Myosin Type II / metabolism
  • Myosin Type II / physiology*
  • Nocodazole / pharmacology
  • Protein Serine-Threonine Kinases / antagonists & inhibitors
  • Protein Serine-Threonine Kinases / metabolism
  • Staurosporine / pharmacology
  • Ubiquitin / metabolism

Substances

  • Contractile Proteins
  • Enzyme Inhibitors
  • Heterocyclic Compounds, 4 or More Rings
  • KIF11 protein, human
  • Leupeptins
  • Ubiquitin
  • anillin
  • blebbistatin
  • Aurora Kinases
  • Protein Serine-Threonine Kinases
  • Cyclin-Dependent Kinases
  • Myosin Type II
  • Kinesins
  • Staurosporine
  • benzyloxycarbonylleucyl-leucyl-leucine aldehyde
  • Nocodazole