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PMID: 16103226 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

An ECT2-centralspindlin complex regulates the localization and function of RhoA.

The Journal of cell biology ·Vol. 170 ·No. 4 ·2005-08-15 ·Pages 571-82

Yüce O, Piekny A, Glotzer M

Abstract

In anaphase, the spindle dictates the site of contractile ring assembly. Assembly and ingression of the contractile ring involves activation of myosin-II and actin polymerization, which are triggered by the GTPase RhoA. In many cells, the central spindle affects division plane positioning via unknown molecular mechanisms. Here, we dissect furrow formation in human cells and show that the RhoGEF ECT2 is required for cortical localization of RhoA and contractile ring assembly. ECT2 concentrates on the central spindle by binding to centralspindlin. Depletion of the centralspindlin component MKLP1 prevents central spindle localization of ECT2; however, RhoA, F-actin, and myosin still accumulate on the equatorial cell cortex. Depletion of the other centralspindlin component, CYK-4/MgcRacGAP, prevents cortical accumulation of RhoA, F-actin, and myosin. CYK-4 and ECT2 interact, and this interaction is cell cycle regulated via ECT2 phosphorylation. Thus, central spindle localization of ECT2 assists division plane positioning and the CYK-4 subunit of centralspindlin acts upstream of RhoA to promote furrow assembly.

MeSH Terms
Actins/metabolism Anaphase/drug effects Aurora Kinases Cell Cycle Proteins/metabolism Cytokinesis/drug effects Enzyme Activation/drug effects Enzyme Inhibitors/pharmacology HeLa Cells Humans Metaphase/drug effects Microtubule-Associated Proteins/metabolism Models, Biological Multiprotein Complexes/metabolism Myosin Type II/metabolism Phenotype Phosphorylation/drug effects Protein Binding/drug effects Protein Serine-Threonine Kinases/antagonists & inhibitors Protein Transport/drug effects Proto-Oncogene Proteins/metabolism Spindle Apparatus/drug effects,enzymology rhoA GTP-Binding Protein/metabolism
Chemicals
Actins Cell Cycle Proteins ECT2 protein, human Enzyme Inhibitors KIF23 protein, human Microtubule-Associated Proteins Multiprotein Complexes Proto-Oncogene Proteins Aurora Kinases Protein Serine-Threonine Kinases Myosin Type II rhoA GTP-Binding Protein
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Yüce Ozlem
Research Institute of Molecular Pathology, 1030, Vienna, Austria.
Piekny Alisa
Glotzer Michael
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41 references, click to expand
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200501097
Published
2005-08-15
Pages
571-82
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2171506
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.200501097 PMC Full Text View journal details
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