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PMID: 12952075 Published · ppublish English Journal Article Review

Signaling pathways at the leading edge of chemotaxing cells.

Journal of muscle research and cell motility ·Vol. 23 ·No. 7-8 ·2002-00-00 ·Pages 773-9

Chung CY, Firtel RA

Abstract

Chemotaxis, or directed cell movement towards small molecule ligands, is a central function of many cell types and plays a key role in diverse biological processes. This review summarizes our present understanding of the signaling pathways that control the ability of cells to sense the chemoattractant gradient and respond by converting a shallow extracellular gradient into a steep intracellular gradient that leads to formation of a pseudopod in the direction of the chemoattractant gradient and contraction of the cell's posterior. The review focuses on the phosphatidylinositol 3-kinase pathway in Dictyostelium and our understanding of parallel pathways in leukocytes.

MeSH Terms
Animals Cell Division/drug effects Chemotaxis/physiology Dictyostelium/cytology,genetics,physiology Models, Biological Phosphatidylinositol 3-Kinases/metabolism Signal Transduction/physiology
Chemicals
Phosphatidylinositol 3-Kinases
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Chung Chang Y
Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232-6600, USA.
Firtel Richard A
References (47)
47 references, click to expand
  1. PTEN and myotubularin: novel phosphoinositide phosphatases.
    Annu Rev Biochem. 2001;70:247-79 PMID: 11395408
  2. CRAC, a cytosolic protein containing a pleckstrin homology domain, is required for receptor and G protein-mediated activation of adenylyl cyclase in Dictyostelium.
    J Cell Biol. 1994 Sep;126(6):1537-45 PMID: 8089184
  3. Spatial and temporal regulation of 3-phosphoinositides by PI 3-kinase and PTEN mediates chemotaxis.
    Cell. 2002 May 31;109 (5):611-23 PMID: 12062104
  4. Localization of the G protein betagamma complex in living cells during chemotaxis.
    Science. 2000 Feb 11;287(5455):1034-6 PMID: 10669414
  5. Signaling through chemoattractant receptors in Dictyostelium.
    Trends Genet. 1996 Feb;12(2):52-7 PMID: 8851971
  6. Control of cell polarity and chemotaxis by Akt/PKB and PI3 kinase through the regulation of PAKa.
    Mol Cell. 2001 May;7(5):937-47 PMID: 11389841
  7. Role of phosphatidylinositol 3' kinase and a downstream pleckstrin homology domain-containing protein in controlling chemotaxis in dictyostelium.
    J Cell Biol. 2001 May 14;153(4):795-810 PMID: 11352940
  8. In vivo observations of myosin II dynamics support a role in rear retraction.
    Mol Biol Cell. 1999 May;10(5):1309-23 PMID: 10233146
  9. 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
  10. Chemoattractant and GTP gamma S-mediated stimulation of adenylyl cyclase in Dictyostelium requires translocation of CRAC to membranes.
    J Cell Biol. 1995 Jun;129(6):1659-65 PMID: 7790361
  11. Chemotaxis in eukaryotic cells: a focus on leukocytes and Dictyostelium.
    Annu Rev Cell Biol. 1988;4:649-86 PMID: 2848555
  12. G protein signaling events are activated at the leading edge of chemotactic cells.
    Cell. 1998 Oct 2;95(1):81-91 PMID: 9778249
  13. Lipid products of PI(3)Ks maintain persistent cell polarity and directed motility in neutrophils.
    Nat Cell Biol. 2002 Jul;4(7):513-8 PMID: 12080345
  14. Central role for G protein-coupled phosphoinositide 3-kinase gamma in inflammation.
    Science. 2000 Feb 11;287(5455):1049-53 PMID: 10669418
  15. Signal transduction in neutrophil chemotaxis.
    Biochemistry (Mosc). 2001 Apr;66(4):351-68 PMID: 11403641
  16. Dynamics of a chemoattractant receptor in living neutrophils during chemotaxis.
    Mol Biol Cell. 1999 Apr;10(4):1163-78 PMID: 10198064
  17. Function of PI3Kgamma in thymocyte development, T cell activation, and neutrophil migration.
    Science. 2000 Feb 11;287(5455):1040-6 PMID: 10669416
  18. Roles of PLC-beta2 and -beta3 and PI3Kgamma in chemoattractant-mediated signal transduction.
    Science. 2000 Feb 11;287(5455):1046-9 PMID: 10669417
  19. Neutrophils lacking phosphoinositide 3-kinase gamma show loss of directionality during N-formyl-Met-Leu-Phe-induced chemotaxis.
    Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3603-8 PMID: 11904423
  20. Directional guidance of neuronal migration in the olfactory system by the protein Slit.
    Nature. 1999 Jul 22;400(6742):331-6 PMID: 10432110
  21. The molecular genetics of chemotaxis: sensing and responding to chemoattractant gradients.
    Bioessays. 2000 Jul;22(7):603-15 PMID: 10878573
  22. Lamellipodial localization of Dictyostelium myosin heavy chain kinase A is mediated via F-actin binding by the coiled-coil domain.
    FEBS Lett. 2002 Apr 10;516(1-3):58-62 PMID: 11959103
  23. 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
  24. Dynamic distribution of chemoattractant receptors in living cells during chemotaxis and persistent stimulation.
    J Cell Biol. 1997 Oct 20;139(2):365-74 PMID: 9334341
  25. Integration of signaling networks that regulate Dictyostelium differentiation.
    Annu Rev Cell Dev Biol. 1999;15:469-517 PMID: 10611970
  26. Spatial sensing in fibroblasts mediated by 3' phosphoinositides.
    J Cell Biol. 2000 Dec 11;151(6):1269-80 PMID: 11121441
  27. Mechanisms of leukocyte motility and chemotaxis.
    Curr Opin Immunol. 1994 Feb;6(1):113-24 PMID: 8172673
  28. A novel Akt/PKB-related kinase is essential for morphogenesis in Dictyostelium.
    Curr Biol. 2000 Jun 15;10(12):708-17 PMID: 10873800
  29. A cell's sense of direction.
    Science. 1999 Apr 30;284(5415):765-70 PMID: 10221901
  30. 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
  31. A PtdInsP(3)- and Rho GTPase-mediated positive feedback loop regulates neutrophil polarity.
    Nat Cell Biol. 2002 Jul;4(7):509-13 PMID: 12080346
  32. Dictyostelium myosin heavy chain phosphorylation sites regulate myosin filament assembly and localization in vivo.
    Cell. 1993 Oct 22;75(2):363-71 PMID: 7691416
  33. Tumor suppressor PTEN mediates sensing of chemoattractant gradients.
    Cell. 2002 May 31;109 (5):599-610 PMID: 12062103
  34. Mechanism of action and in vivo role of platelet-derived growth factor.
    Physiol Rev. 1999 Oct;79(4):1283-316 PMID: 10508235
  35. Rac regulates phosphorylation of the myosin-II heavy chain, actinomyosin disassembly and cell spreading.
    Nat Cell Biol. 1999 Aug;1(4):242-8 PMID: 10559923
  36. Disruption of a single Pten allele augments the chemotactic response of B lymphocytes to stromal cell-derived factor-1.
    J Immunol. 2002 Jul 1;169(1):49-54 PMID: 12077227
  37. Leukocytes navigate by compass: roles of PI3Kgamma and its lipid products.
    Trends Cell Biol. 2000 Nov;10(11):466-73 PMID: 11050418
  38. Polarization of chemoattractant receptor signaling during neutrophil chemotaxis.
    Science. 2000 Feb 11;287(5455):1037-40 PMID: 10669415
  39. Distinct PI(3)Ks mediate mitogenic signalling and cell migration in macrophages.
    Nat Cell Biol. 1999 May;1(1):69-71 PMID: 10559867
  40. Molecular genetics of signal transduction in Dictyostelium.
    Annu Rev Biochem. 1996;65:411-40 PMID: 8811185
  41. 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
  42. Roles of PI3Ks in leukocyte chemotaxis and phagocytosis.
    Curr Opin Cell Biol. 2002 Apr;14(2):203-13 PMID: 11891120
  43. The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate.
    J Biol Chem. 1998 May 29;273(22):13375-8 PMID: 9593664
  44. Temporal and spatial regulation of chemotaxis.
    Dev Cell. 2002 Oct;3(4):469-78 PMID: 12408799
  45. Signaling pathways controlling cell polarity and chemotaxis.
    Trends Biochem Sci. 2001 Sep;26(9):557-66 PMID: 11551793
  46. A phosphatidylinositol (PI) kinase gene family in Dictyostelium discoideum: biological roles of putative mammalian p110 and yeast Vps34p PI 3-kinase homologs during growth and development.
    Mol Cell Biol. 1995 Oct;15(10):5645-56 PMID: 7565716
  47. Crossing the midline: roles and regulation of Robo receptors.
    Neuron. 2000 Dec;28(3):767-77 PMID: 11163265
Article Info
Journal
Journal of muscle research and cell motility
Abbr.
J Muscle Res Cell Motil
ISSN
0142-4319
Published
2002-00-00
Pages
773-9
Language
English
Region
Netherlands
NLM ID
8006298
Subset
IM
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