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.
© 2019 Adriaans et al.
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