Dissecting temporal and spatial control of cytokinesis with a myosin II Inhibitor.
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.
Straight
Aaron F
AF
Department of Cell Biology and Institute of Chemistry and Cell Biology, Harvard Medical School, 250 Longwood Avenue, Boston, MA 02115, USA. aaron_straight@hms.harvard.edu
Cheung
Amy
A
Limouze
John
J
Chen
Irene
I
Westwood
Nick J
NJ
Sellers
James R
JR
Mitchison
Timothy J
TJ
D000705:Anaphase; D064127:Aurora Kinases; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003285:Contractile Proteins / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004261:DNA Replication; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006367:HeLa Cells; D006576:Heterocyclic Compounds, 4 or More Rings / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D016547:Kinesins / Q000378:metabolism; D007976:Leupeptins / Q000494:pharmacology; D008870:Microtubules / Q000502:physiology; D008938:Mitosis / Q000187:drug effects; D024462:Myosin Type II / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology*; D015739:Nocodazole / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D019311:Staurosporine / Q000494:pharmacology; D025801:Ubiquitin / Q000378:metabolism
D003285:Contractile Proteins; D004791:Enzyme Inhibitors; D006576:Heterocyclic Compounds, 4 or More Rings; C470243:KIF11 protein, human; D007976:Leupeptins; D025801:Ubiquitin; C095886:anillin; C472645:blebbistatin; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D018844:Cyclin-Dependent Kinases; D024462:Myosin Type II; D016547:Kinesins; D019311:Staurosporine; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde; D015739:Nocodazole