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PMID: 10805781 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Role of Rac in controlling the actin cytoskeleton and chemotaxis in motile cells.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 97 ·No. 10 ·2000-05-09 ·Pages 5225-30

Chung CY, Lee S, Briscoe C, Ellsworth C, Firtel RA

Abstract

We have used the chemotactic ability of Dictyostelium cells to examine the roles of Rho family members, known regulators of the assembly of F-actin, in cell movement. Wild-type cells polarize with a leading edge enriched in F-actin toward a chemoattractant. Overexpression of constitutively active Dictyostelium Rac1B(61L) or disruption of DdRacGAP1, which encodes a Dictyostelium Rac1 GAP, induces membrane ruffles enriched with actin filaments around the perimeter of the cell and increased levels of F-actin in resting cells. Whereas wild-type cells move linearly toward the cAMP source, Rac1B(61L) and Ddracgap1 null cells make many wrong turns and chemotaxis is inefficient, which presumably results from the unregulated activation of F-actin assembly and pseudopod extension. Cells expressing dominant-negative DdRac1B(17N) do not have a well-defined F-actin-rich leading edge and do not protrude pseudopodia, resulting in very poor cell motility. From these studies and assays examining chemoattractant-mediated F-actin assembly, we suggest DdRac1 regulates the basal levels of F-actin assembly, its dynamic reorganization in response to chemoattractants, and cellular polarity during chemotaxis.

MeSH Terms
Actins/physiology Animals Cell Aggregation Chemotaxis/physiology Cyclic AMP/physiology Cytoskeleton/physiology,ultrastructure Dictyostelium/genetics,physiology Image Processing, Computer-Assisted rac1 GTP-Binding Protein/genetics,metabolism
Chemicals
Actins Cyclic AMP rac1 GTP-Binding Protein
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Chung C Y
Section of Cell and Developmental Biology, Division of Biology, Center for Molecular Genetics, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0634, USA.
Lee S
Briscoe C
Ellsworth C
Firtel R A
References (42)
42 references, click to expand
  1. Life at the leading edge: the formation of cell protrusions.
    Annu Rev Cell Biol. 1993;9:411-44 PMID: 8280467
  2. Cloning and characterization of a rhoGAP homolog from Dictyostelium discoideum.
    J Biol Chem. 1997 Jun 20;272(25):15682-6 PMID: 9188459
  3. Cloning and characterization of the G-box binding factor, an essential component of the developmental switch between early and late development in Dictyostelium.
    Genes Dev. 1994 Feb 15;8(4):502-14 PMID: 8125261
  4. Mechanisms of leukocyte motility and chemotaxis.
    Curr Opin Immunol. 1994 Feb;6(1):113-24 PMID: 8172673
  5. Regulation of cortical actin cytoskeleton assembly during polarized cell growth in budding yeast.
    J Cell Biol. 1995 Feb;128(4):599-615 PMID: 7860633
  6. Chemoattractant-controlled accumulation of coronin at the leading edge of Dictyostelium cells monitored using a green fluorescent protein-coronin fusion protein.
    Curr Biol. 1995 Nov 1;5(11):1280-5 PMID: 8574585
  7. Origins of cell polarity.
    Cell. 1996 Feb 9;84(3):335-44 PMID: 8608587
  8. The aimless RasGEF is required for processing of chemotactic signals through G-protein-coupled receptors in Dictyostelium.
    Curr Biol. 1996 Jun 1;6(6):719-29 PMID: 8793298
  9. Myosin structure and function.
    Cold Spring Harb Symp Quant Biol. 1995;60:783-91 PMID: 8824453
  10. Signaling through chemoattractant receptors in Dictyostelium.
    Trends Genet. 1996 Feb;12(2):52-7 PMID: 8851971
  11. Rho, Rac and Cdc42 GTPases regulate the organization of the actin cytoskeleton.
    Curr Opin Cell Biol. 1997 Feb;9(1):86-92 PMID: 9013670
  12. Fluid-phase uptake by macropinocytosis in Dictyostelium.
    J Cell Sci. 1997 Jan;110 ( Pt 2):105-12 PMID: 9044041
  13. Inactivation of two Dictyostelium discoideum genes, DdPIK1 and DdPIK2, encoding proteins related to mammalian phosphatidylinositide 3-kinases, results in defects in endocytosis, lysosome to postlysosome transport, and actin cytoskeleton organization.
    J Cell Biol. 1997 Mar 24;136(6):1271-86 PMID: 9087443
  14. Regulation of actin polymerization in cell-free systems by GTPgammaS and Cdc42.
    J Cell Biol. 1997 Jul 28;138(2):363-74 PMID: 9230078
  15. cGMP as second messenger during Dictyostelium chemotaxis.
    FEBS Lett. 1997 Jun 23;410(1):25-8 PMID: 9247116
  16. Migration responses of human monocytic cell lines to alpha- and beta-chemokines.
    Cytokine. 1997 Jul;9(7):521-8 PMID: 9237815
  17. The Dictyostelium MAP kinase kinase DdMEK1 regulates chemotaxis and is essential for chemoattractant-mediated activation of guanylyl cyclase.
    EMBO J. 1997 Jul 16;16(14):4317-32 PMID: 9250676
  18. Dictyostelium RasG is required for normal motility and cytokinesis, but not growth.
    J Cell Biol. 1997 Aug 11;138(3):605-14 PMID: 9245789
  19. Disruption of Dictyostelium PI3K genes reduces [32P]phosphatidylinositol 3,4 bisphosphate and [32P]phosphatidylinositol trisphosphate levels, alters F-actin distribution and impairs pinocytosis.
    J Cell Sci. 1998 Jan;111 ( Pt 2):283-94 PMID: 9405319
  20. Receptors induce chemotaxis by releasing the betagamma subunit of Gi, not by activating Gq or Gs.
    Proc Natl Acad Sci U S A. 1997 Dec 23;94(26):14489-94 PMID: 9405640
  21. DRhoGEF2 encodes a member of the Dbl family of oncogenes and controls cell shape changes during gastrulation in Drosophila.
    Genes Dev. 1998 Jan 15;12(2):274-84 PMID: 9436986
  22. Rho GTPases and the actin cytoskeleton.
    Science. 1998 Jan 23;279(5350):509-14 PMID: 9438836
  23. A role for Cdc42 in macrophage chemotaxis.
    J Cell Biol. 1998 Jun 1;141(5):1147-57 PMID: 9606207
  24. Chemokines and chemotaxis of leukocytes in infectious meningitis.
    J Neuroimmunol. 1998 May 1;85(1):33-43 PMID: 9626995
  25. Phagocyte chemoattractant receptors.
    Ann N Y Acad Sci. 1997 Dec 15;832:69-84 PMID: 9704038
  26. G protein signaling events are activated at the leading edge of chemotactic cells.
    Cell. 1998 Oct 2;95(1):81-91 PMID: 9778249
  27. A computer-assisted system for reconstructing and interpreting the dynamic three-dimensional relationships of the outer surface, nucleus and pseudopods of crawling cells.
    Cell Motil Cytoskeleton. 1998;41(3):225-46 PMID: 9829777
  28. Rho GTPases control polarity, protrusion, and adhesion during cell movement.
    J Cell Biol. 1999 Mar 22;144(6):1235-44 PMID: 10087266
  29. Chemoattractant-mediated transient activation and membrane localization of Akt/PKB is required for efficient chemotaxis to cAMP in Dictyostelium.
    EMBO J. 1999 Apr 15;18(8):2092-105 PMID: 10205164
  30. A cell's sense of direction.
    Science. 1999 Apr 30;284(5415):765-70 PMID: 10221901
  31. A novel Ras-interacting protein required for chemotaxis and cyclic adenosine monophosphate signal relay in Dictyostelium.
    Mol Biol Cell. 1999 Sep;10(9):2829-45 PMID: 10473630
  32. Dictyostelium as model system for studies of the actin cytoskeleton by molecular genetics.
    Microsc Res Tech. 1999 Oct 15;47(2):124-34 PMID: 10523791
  33. PAKa, a putative PAK family member, is required for cytokinesis and the regulation of the cytoskeleton in Dictyostelium discoideum cells during chemotaxis.
    J Cell Biol. 1999 Nov 1;147(3):559-76 PMID: 10545500
  34. Leucocyte-like motility of cancer cells, with reference to the mechanism of extravasation in metastasis.
    Gan. 1979 Aug;70(4):559-61 PMID: 510854
  35. Relationship of pseudopod extension to chemotactic hormone-induced actin polymerization in amoeboid cells.
    J Cell Biochem. 1988 Jul;37(3):285-99 PMID: 3410887
  36. Identification of actin nucleation activity and polymerization inhibitor in ameboid cells: their regulation by chemotactic stimulation.
    J Cell Biol. 1989 Nov;109(5):2207-13 PMID: 2553744
  37. Transduction of the chemotactic signal to the actin cytoskeleton of Dictyostelium discoideum.
    Dev Biol. 1989 Dec;136(2):517-25 PMID: 2511051
  38. Molecular genetic analysis of two G alpha protein subunits in Dictyostelium.
    J Biol Chem. 1991 Jan 15;266(2):1220-8 PMID: 1670774
  39. Analysis of G alpha 4, a G-protein subunit required for multicellular development in Dictyostelium.
    Genes Dev. 1992 Jan;6(1):38-49 PMID: 1730409
  40. The small GTP-binding protein rac regulates growth factor-induced membrane ruffling.
    Cell. 1992 Aug 7;70(3):401-10 PMID: 1643658
  41. Independent control of locomotion and orientation during Dictyostelium discoideum chemotaxis.
    J Cell Sci. 1992 Aug;102 ( Pt 4):763-8 PMID: 1331131
  42. Cloning and characterization of seven novel Dictyostelium discoideum rac-related genes belonging to the rho family of GTPases.
    Gene. 1993 Dec 22;136(1-2):61-8 PMID: 8294042
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.97.10.5225
Published
2000-05-09
Pages
5225-30
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC25810
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.97.10.5225 PMC Full Text View journal details
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