Home LiteratureArticle Details
PMID: 16129829 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

MgcRacGAP controls the assembly of the contractile ring and the initiation of cytokinesis.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 102 ·No. 37 ·2005-09-13 ·Pages 13158-63

Zhao WM, Fang G

Abstract

Initiation of cytokinesis requires the establishment of the cleavage plane, the assembly of the contractile ring, and the ingression of the cleavage furrow. MgcRacGAP, a GTPase-activating protein for RhoA, is required for cytokinesis, but the mechanism of its action remains unknown. We report here that MgcRacGAP is required for the assembly of anillin and myosin into the contractile ring. In addition, MgcRacGAP is required for the localized activation of myosin through the RhoA-mediated phosphorylation of the myosin regulatory light chain. Cells with MgcRacGAP RNA interference (RNAi) failed cytokinesis without any ingression of the cleavage furrow. Paradoxically, MgcRacGAP, a GTPase-activating protein, associates during cytokinesis with ECT2, a guanine nucleotide exchange factor for RhoA, and the localization of ECT2 to both the central spindle and the contractile ring depends on MgcRacGAP. Knockdown of ECT2 phenocopies that of MgcRacGAP. We conclude that MgcRacGAP controls the initiation of cytokinesis by regulating ECT2, which in turn induces the assembly of the contractile ring and triggers the ingression of the cleavage furrow.

MeSH Terms
Contractile Proteins/metabolism Cytokinesis Cytoskeleton/metabolism,physiology GTPase-Activating Proteins/genetics,physiology HeLa Cells Humans Myosin Light Chains/metabolism Myosins/metabolism Proto-Oncogene Proteins/metabolism RNA, Small Interfering/pharmacology Spindle Apparatus/metabolism Transfection rhoA GTP-Binding Protein/metabolism
Chemicals
Contractile Proteins ECT2 protein, human GTPase-Activating Proteins Myosin Light Chains Proto-Oncogene Proteins RNA, Small Interfering anillin mgcRacGAP RHOA protein, human Myosins rhoA GTP-Binding Protein
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Zhao Wei-meng
Department of Biological Sciences, Stanford University, Stanford, CA 94305-5020, USA.
Fang Guowei
References (28)
28 references, click to expand
  1. MgcRacGAP is involved in cytokinesis through associating with mitotic spindle and midbody.
    J Biol Chem. 2001 Feb 23;276(8):5821-8 PMID: 11085985
  2. Rho-kinase/ROCK is involved in cytokinesis through the phosphorylation of myosin light chain and not ezrin/radixin/moesin proteins at the cleavage furrow.
    Oncogene. 2000 Dec 7;19(52):6059-64 PMID: 11146558
  3. A system for stable expression of short interfering RNAs in mammalian cells.
    Science. 2002 Apr 19;296(5567):550-3 PMID: 11910072
  4. Molecular dissection of cytokinesis by RNA interference in Drosophila cultured cells.
    Mol Biol Cell. 2002 Jul;13(7):2448-60 PMID: 12134082
  5. A RhoGEF and Rho family GTPase-activating protein complex links the contractile ring to cortical microtubules at the onset of cytokinesis.
    Dev Cell. 2003 Jan;4(1):29-39 PMID: 12530961
  6. Dissecting temporal and spatial control of cytokinesis with a myosin II Inhibitor.
    Science. 2003 Mar 14;299(5613):1743-7 PMID: 12637748
  7. Phosphorylation by aurora B converts MgcRacGAP to a RhoGAP during cytokinesis.
    Dev Cell. 2003 Apr;4(4):549-60 PMID: 12689593
  8. Citron kinase, a Rho-dependent kinase, induces di-phosphorylation of regulatory light chain of myosin II.
    Mol Biol Cell. 2003 May;14(5):1745-56 PMID: 12802051
  9. Animal cell division: a fellowship of the double ring?
    J Cell Sci. 2003 Nov 1;116(Pt 21):4277-81 PMID: 14514883
  10. Spatial and temporal pathway for assembly and constriction of the contractile ring in fission yeast cytokinesis.
    Dev Cell. 2003 Nov;5(5):723-34 PMID: 14602073
  11. Cleavage furrow positioning.
    J Cell Biol. 2004 Feb 2;164(3):347-51 PMID: 14757750
  12. Mutations in orbit/mast reveal that the central spindle is comprised of two microtubule populations, those that initiate cleavage and those that propagate furrow ingression.
    J Cell Biol. 2004 Jul 5;166(1):49-60 PMID: 15240569
  13. Cell cycle regulation of central spindle assembly.
    Nature. 2004 Aug 19;430(7002):908-13 PMID: 15282614
  14. Disruption of the Dictyostelium myosin heavy chain gene by homologous recombination.
    Science. 1987 May 29;236(4805):1086-91 PMID: 3576222
  15. Oncogene ect2 is related to regulators of small GTP-binding proteins.
    Nature. 1993 Apr 1;362(6419):462-5 PMID: 8464478
  16. In vivo phosphorylation of regulatory light chain of myosin II during mitosis of cultured cells.
    J Cell Biol. 1994 Jan;124(1-2):129-37 PMID: 8294496
  17. A requirement for Rho and Cdc42 during cytokinesis in Xenopus embryos.
    Curr Biol. 1997 Jan 1;7(1):12-23 PMID: 8999996
  18. Direct binding of CDC20 protein family members activates the anaphase-promoting complex in mitosis and G1.
    Mol Cell. 1998 Aug;2(2):163-71 PMID: 9734353
  19. Immunofluorescence detection of ezrin/radixin/moesin (ERM) proteins with their carboxyl-terminal threonine phosphorylated in cultured cells and tissues.
    J Cell Sci. 1999 Apr;112 ( Pt 8):1149-58 PMID: 10085250
  20. A putative exchange factor for Rho1 GTPase is required for initiation of cytokinesis in Drosophila.
    Genes Dev. 1999 Sep 1;13(17):2301-14 PMID: 10485851
  21. Ect2 and MgcRacGAP regulate the activation and function of Cdc42 in mitosis.
    J Cell Biol. 2005 Jan 17;168(2):221-32 PMID: 15642749
  22. The tandem BRCT domains of Ect2 are required for both negative and positive regulation of Ect2 in cytokinesis.
    J Biol Chem. 2005 Feb 18;280(7):5733-9 PMID: 15545273
  23. Human ECT2 is an exchange factor for Rho GTPases, phosphorylated in G2/M phases, and involved in cytokinesis.
    J Cell Biol. 1999 Nov 29;147(5):921-8 PMID: 10579713
  24. Accumulation of GTP-bound RhoA during cytokinesis and a critical role of ECT2 in this accumulation.
    J Biol Chem. 2000 Jun 9;275(23):17233-6 PMID: 10837491
  25. CYK-4: A Rho family gtpase activating protein (GAP) required for central spindle formation and cytokinesis.
    J Cell Biol. 2000 Jun 26;149(7):1391-404 PMID: 10871280
  26. Functional analysis of a human homologue of the Drosophila actin binding protein anillin suggests a role in cytokinesis.
    J Cell Biol. 2000 Aug 7;150(3):539-52 PMID: 10931866
  27. Effects of the regulatory light chain phosphorylation of myosin II on mitosis and cytokinesis of mammalian cells.
    J Biol Chem. 2000 Nov 3;275(44):34512-20 PMID: 10944522
  28. Central spindle assembly and cytokinesis require a kinesin-like protein/RhoGAP complex with microtubule bundling activity.
    Dev Cell. 2002 Jan;2(1):41-54 PMID: 11782313
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0504145102
Published
2005-09-13
Epub
2005-00-29
Pages
13158-63
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC1201590
Subset
IM
Grants
NIGMS NIH HHS · R01 GM062852 · United States
NIGMS NIH HHS · GM062852 · United States
External Links
PubMed source DOI: 10.1073/pnas.0504145102 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2