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PMID: 15240570 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Mutations in sticky lead to defective organization of the contractile ring during cytokinesis and are enhanced by Rho and suppressed by Rac.

The Journal of cell biology ·Vol. 166 ·No. 1 ·2004-07-05 ·Pages 61-71

D'Avino PP, Savoian MS, Glover DM

Abstract

The contractile ring is a highly dynamic structure, but how this dynamism is accomplished remains unclear. Here, we report the identification and analysis of a novel Drosophila gene, sticky (sti), essential for cytokinesis in all fly proliferating tissues. sti encodes the Drosophila orthologue of the mammalian Citron kinase. RNA interference-mediated silencing of sti in cultured cells causes them to become multinucleate. Components of the contractile ring and central spindle are recruited normally in such STICKY-depleted cells that nevertheless display asymmetric furrowing and aberrant blebbing. Together with an unusual distribution of F-actin and Anillin, these phenotypes are consistent with defective organization of the contractile ring. sti shows opposite genetic interactions with Rho and Rac genes suggesting that these GTPases antagonistically regulate STICKY functions. Similar genetic evidence indicates that RacGAP50C inhibits Rac during cytokinesis. We discuss that antagonism between Rho and Rac pathways may control contractile ring dynamics during cytokinesis.

MeSH Terms
Actins/biosynthesis Alleles Animals Animals, Genetically Modified Blotting, Western Cell Division Cell Nucleus/metabolism Cell Separation Cloning, Molecular Contractile Proteins/biosynthesis Drosophila Flow Cytometry GTP Phosphohydrolases/metabolism Gene Silencing Genetic Complementation Test Intracellular Signaling Peptides and Proteins Mitosis Models, Biological Models, Genetic Mutation Phenotype Polyploidy Protein Serine-Threonine Kinases/genetics,physiology RNA Interference rac GTP-Binding Proteins/metabolism rho GTP-Binding Proteins/metabolism
Chemicals
Actins Contractile Proteins Intracellular Signaling Peptides and Proteins anillin citron-kinase Protein Serine-Threonine Kinases GTP Phosphohydrolases rac GTP-Binding Proteins rho GTP-Binding Proteins
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
D'Avino Pier Paolo
Cancer Research UK Cell Cycle Genetics Research Group, Department of Genetics, University of Cambridge, Downing Site, CB2 3EH. [email protected]
Savoian Matthew S
Glover David M
References (61)
61 references, click to expand
  1. Cytokinesis in eukaryotes: a mechanistic comparison.
    Curr Opin Cell Biol. 1999 Feb;11(1):68-80 PMID: 10047527
  2. The small GTP-binding protein rho regulates cortical activities in cultured cells during division.
    J Cell Biol. 1999 Jan 25;144(2):305-13 PMID: 9922456
  3. 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
  4. 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
  5. Untying the Gordian knot of cytokinesis. Role of small G proteins and their regulators.
    J Cell Biol. 2000 Mar 6;148(5):843-8 PMID: 10704435
  6. Towards a molecular understanding of cytokinesis.
    Trends Cell Biol. 2000 Jun;10(6):228-37 PMID: 10802538
  7. Citron, a Rho target that affects contractility during cytokinesis.
    Microsc Res Tech. 2000 Apr 15;49(2):123-6 PMID: 10816250
  8. 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
  9. Defective neurogenesis in citron kinase knockout mice by altered cytokinesis and massive apoptosis.
    Neuron. 2000 Oct;28(1):115-27 PMID: 11086988
  10. 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
  11. Drosophila aurora B kinase is required for histone H3 phosphorylation and condensin recruitment during chromosome condensation and to organize the central spindle during cytokinesis.
    J Cell Biol. 2001 Feb 19;152(4):669-82 PMID: 11266459
  12. Drosophila Rho-associated kinase (Drok) links Frizzled-mediated planar cell polarity signaling to the actin cytoskeleton.
    Cell. 2001 Apr 6;105(1):81-91 PMID: 11301004
  13. Rho-dependent transfer of Citron-kinase to the cleavage furrow of dividing cells.
    J Cell Sci. 2001 Sep;114(Pt 18):3273-84 PMID: 11591816
  14. Regulating axon branch stability: the role of p190 RhoGAP in repressing a retraction signaling pathway.
    Cell. 2001 Oct 19;107(2):195-207 PMID: 11672527
  15. Animal cell cytokinesis.
    Annu Rev Cell Dev Biol. 2001;17:351-86 PMID: 11687493
  16. Three C. elegans Rac proteins and several alternative Rac regulators control axon guidance, cell migration and apoptotic cell phagocytosis.
    Development. 2001 Nov;128(22):4475-88 PMID: 11714673
  17. 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
  18. RNAi triggered by symmetrically transcribed transgenes in Drosophila melanogaster.
    Genetics. 2002 Feb;160(2):637-48 PMID: 11861567
  19. Domains of the Pavarotti kinesin-like protein that direct its subcellular distribution: effects of mislocalisation on the tubulin and actin cytoskeleton during Drosophila oogenesis.
    J Cell Sci. 2002 Feb 15;115(Pt 4):725-36 PMID: 11865028
  20. Rac function and regulation during Drosophila development.
    Nature. 2002 Mar 28;416(6879):438-42 PMID: 11919634
  21. Rac GTPases control axon growth, guidance and branching.
    Nature. 2002 Mar 28;416(6879):442-7 PMID: 11919635
  22. Role of MgcRacGAP/Cyk4 as a regulator of the small GTPase Rho family in cytokinesis and cell differentiation.
    Cell Struct Funct. 2001 Dec;26(6):645-51 PMID: 11942621
  23. Rho-binding kinase (LET-502) and myosin phosphatase (MEL-11) regulate cytokinesis in the early Caenorhabditis elegans embryo.
    J Cell Sci. 2002 Jun 1;115(Pt 11):2271-82 PMID: 12006612
  24. Molecular dissection of cytokinesis by RNA interference in Drosophila cultured cells.
    Mol Biol Cell. 2002 Jul;13(7):2448-60 PMID: 12134082
  25. Constitutive active GTPases Rac and Cdc42 are associated with endoreplication in PAE cells.
    Eur J Cancer. 2002 Sep;38(13):1775-82 PMID: 12175695
  26. Essential role of citron kinase in cytokinesis of spermatogenic precursors.
    J Cell Sci. 2002 Dec 15;115(Pt 24):4819-26 PMID: 12432070
  27. RAC2 GTPase deficiency and myeloid cell dysfunction in human and mouse.
    J Pediatr Hematol Oncol. 2002 Dec;24(9):791-4 PMID: 12468931
  28. 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
  29. Finishing a whole-genome shotgun: release 3 of the Drosophila melanogaster euchromatic genome sequence.
    Genome Biol. 2002;3(12):RESEARCH0079 PMID: 12537568
  30. Phosphorylation by aurora B converts MgcRacGAP to a RhoGAP during cytokinesis.
    Dev Cell. 2003 Apr;4(4):549-60 PMID: 12689593
  31. 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
  32. Development, plasticity and evolution of butterfly eyespot patterns.
    Nature. 1996 Nov 21;384(6606):236-42 PMID: 12809139
  33. Activity of Rho-family GTPases during cell division as visualized with FRET-based probes.
    J Cell Biol. 2003 Jul 21;162(2):223-32 PMID: 12860967
  34. Rho and Rac take center stage.
    Cell. 2004 Jan 23;116(2):167-79 PMID: 14744429
  35. Phosphorylation of smooth muscle myosin at two distinct sites by myosin light chain kinase.
    J Biol Chem. 1985 Aug 25;260(18):10027-31 PMID: 3839510
  36. Genes controlling essential cell-cycle functions in Drosophila melanogaster.
    Genes Dev. 1989 Apr;3(4):438-53 PMID: 2498166
  37. Interphase nuclear envelope lamins form a discontinuous network that interacts with only a fraction of the chromatin in the nuclear periphery.
    Cell. 1990 Jul 13;62(1):89-106 PMID: 2194675
  38. Targeted gene expression as a means of altering cell fates and generating dominant phenotypes.
    Development. 1993 Jun;118(2):401-15 PMID: 8223268
  39. A Drosophila homologue of membrane-skeleton protein 4.1 is associated with septate junctions and is encoded by the coracle gene.
    Development. 1994 Mar;120(3):545-57 PMID: 8162854
  40. The Drosophila peanut gene is required for cytokinesis and encodes a protein similar to yeast putative bud neck filament proteins.
    Cell. 1994 May 6;77(3):371-9 PMID: 8181057
  41. Diaphanous is required for cytokinesis in Drosophila and shares domains of similarity with the products of the limb deformity gene.
    Development. 1994 Dec;120(12):3367-77 PMID: 7821209
  42. The role of the BR-C locus on the expression of genes located at the ecdysone-regulated 3C puff of Drosophila melanogaster.
    Mech Dev. 1995 Feb;49(3):161-71 PMID: 7734390
  43. Anillin, a contractile ring protein that cycles from the nucleus to the cell cortex.
    J Cell Biol. 1995 Oct;131(1):165-78 PMID: 7559773
  44. A novel partner for the GTP-bound forms of rho and rac.
    FEBS Lett. 1995 Dec 18;377(2):243-8 PMID: 8543060
  45. Rom1p and Rom2p are GDP/GTP exchange proteins (GEPs) for the Rho1p small GTP binding protein in Saccharomyces cerevisiae.
    EMBO J. 1996 May 1;15(9):2196-207 PMID: 8641285
  46. Phosphorylation and activation of myosin by Rho-associated kinase (Rho-kinase).
    J Biol Chem. 1996 Aug 23;271(34):20246-9 PMID: 8702756
  47. A requirement for Rho and Cdc42 during cytokinesis in Xenopus embryos.
    Curr Biol. 1997 Jan 1;7(1):12-23 PMID: 8999996
  48. The role of RhoA in tissue polarity and Frizzled signalling.
    Nature. 1997 May 15;387(6630):292-5 PMID: 9153394
  49. p140mDia, a mammalian homolog of Drosophila diaphanous, is a target protein for Rho small GTPase and is a ligand for profilin.
    EMBO J. 1997 Jun 2;16(11):3044-56 PMID: 9214622
  50. P-element insertion alleles of essential genes on the third chromosome of Drosophila melanogaster: correlation of physical and cytogenetic maps in chromosomal region 86E-87F.
    Genetics. 1997 Dec;147(4):1697-722 PMID: 9409831
  51. Myosin light chain-activating phosphorylation sites are required for oogenesis in Drosophila.
    J Cell Biol. 1997 Dec 29;139(7):1805-19 PMID: 9412474
  52. The Drosophila eyes absent gene directs ectopic eye formation in a pathway conserved between flies and vertebrates.
    Development. 1997 Dec;124(23):4819-26 PMID: 9428418
  53. Isolation of CaSLN1 and CaNIK1, the genes for osmosensing histidine kinase homologues, from the pathogenic fungus Candida albicans.
    Microbiology. 1998 Feb;144 ( Pt 2):425-32 PMID: 9493379
  54. MgcRacGAP, a new human GTPase-activating protein for Rac and Cdc42 similar to Drosophila rotundRacGAP gene product, is expressed in male germ cells.
    J Biol Chem. 1998 Mar 13;273(11):6019-23 PMID: 9497316
  55. crooked legs encodes a family of zinc finger proteins required for leg morphogenesis and ecdysone-regulated gene expression during Drosophila metamorphosis.
    Development. 1998 May;125(9):1733-45 PMID: 9521911
  56. pavarotti encodes a kinesin-like protein required to organize the central spindle and contractile ring for cytokinesis.
    Genes Dev. 1998 May 15;12(10):1483-94 PMID: 9585508
  57. Pleckstrin homology domains: a common fold with diverse functions.
    Annu Rev Biophys Biomol Struct. 1998;27:503-28 PMID: 9646876
  58. cyk-1: a C. elegans FH gene required for a late step in embryonic cytokinesis.
    J Cell Sci. 1998 Jul 30;111 ( Pt 14):2017-27 PMID: 9645949
  59. Role of citron kinase as a target of the small GTPase Rho in cytokinesis.
    Nature. 1998 Jul 30;394(6692):491-4 PMID: 9697773
  60. Citron rho-interacting kinase, a novel tissue-specific ser/thr kinase encompassing the Rho-Rac-binding protein Citron.
    J Biol Chem. 1998 Nov 6;273(45):29706-11 PMID: 9792683
  61. The role of anillin in meiotic cytokinesis of Drosophila males.
    J Cell Sci. 1999 Jul;112 ( Pt 14):2323-34 PMID: 10381388
Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200402157
Email
[email protected]
Published
2004-07-05
Pages
61-71
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2172139
Subset
IM
Grants
Medical Research Council · G9901264 · United Kingdom
External Links
PubMed source DOI: 10.1083/jcb.200402157 PMC Full Text View journal details
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