Crossref journal-article
Oxford University Press (OUP)
Journal of Leukocyte Biology (286)
Abstract

AbstractWhereas most cells in adult tissues are fixed in place by cell junctions, leukocytes are motile and able to migrate actively through the walls of blood vessels into surrounding tissues. The actin cytoskeleton of these cells plays a central role in locomotion, phagocytosis, and the regulation of cell shape that are crucial elements of neutrophil and monocyte/macrophage function. This review will concentrate on how macrophages in particular control the actin cytoskeleton to generate cell movement and the shape changes required for chemotaxis. It has recently become evident that a complex of seven proteins known as the Arp2/3 complex regulates the assembly of new actin filament networks at the leading front of moving cells. Proteins of the Wiskott-Aldrich Syndrome Protein (WASP) family bind directly to the Arp2/3 complex and stimulate its ability to promote the nucleation of new actin filaments. Upstream of the WASP family proteins, receptor tyrosine kinases, G-protein-coupled receptors, phosphoinositide-3-OH kinase (PI 3-kinase), and the Rho family of GTPases receive and transduce the signals that lead to actin nucleation through WASP-Arp2/3 action. Although many gaps remain in our understanding, we are now in a position to consider completing signaling pathways that are initiated from outside the cell to the actin rearrangements that drive cell motility and chemotaxis.

Bibliography

Jones, G. E. (2000). Cellular signaling in macrophage migration and chemotaxis. Journal of Leukocyte Biology, 68(5), 593–602.

Authors 1
  1. Gareth E Jones (first)
References 108 Referenced 166
  1. 10.1016/S0092-8674(00)81280-5 / Cell / Cell migration: a physically integrated molecular process by Lauffenburger (1996)
  2. 10.1016/S0092-8674(00)81281-7 / Cell / Actin-based cell motility and cell locomotion by Mitchison (1996)
  3. 10.1016/S0955-0674(98)80083-5 / Curr. Opin. Cell Biol. / The modular structure of actin-regulatory proteins by Puius (1998)
  4. {'key': '2023033020111270500_cit-B4', 'first-page': '79', 'article-title': 'Integrin-mediated cell adhesion: the cytoskeletal connection', 'volume': '65', 'author': 'Critchley', 'year': '1999', 'journal-title': 'Biochem. Soc. Symp.'} / Biochem. Soc. Symp. / Integrin-mediated cell adhesion: the cytoskeletal connection by Critchley (1999)
  5. 10.1242/jcs.110.6.707 / J.Cell Sci. / Rho, Rac and Cdc42 regulate actin organization and cell adhesion in macrophages by Allen (1997)
  6. 10.1177/002215549904700107 / J. Histochem. Cytochem. / Cytoskeletal and adhesive structural polarizations accompany IL-13-induced human macrophage fusion by DeFife (1999)
  7. {'key': '2023033020111270500_cit-B7', 'first-page': '831', 'article-title': 'Integrating the actin and vimentin cytoskeletons', 'volume': '146', 'author': 'Correia', 'year': '1999', 'journal-title': 'adhesion-dependent formation of fimbrin-vimentin complexes in macrophages. J. Cell Biol.'} / adhesion-dependent formation of fimbrin-vimentin complexes in macrophages. J. Cell Biol. / Integrating the actin and vimentin cytoskeletons by Correia (1999)
  8. 10.1083/jcb.141.5.1147 / J. Cell Biol. / A role for Cdc42 in macrophage chemotaxis by Allen (1998)
  9. {'key': '2023033020111270500_cit-B9', 'first-page': '233', 'article-title': 'Cell migration as a five-step cycle', 'volume': '65', 'author': 'Sheetz', 'year': '1999', 'journal-title': 'Biochem. Soc. Symp.'} / Biochem. Soc. Symp. / Cell migration as a five-step cycle by Sheetz (1999)
  10. 10.1083/jcb.139.5.1349 / J. Cell Biol. / Multistep navigation and the combinatorial control of leukocyte chemotaxis by Foxman (1997)
  11. {'key': '2023033020111270500_cit-B11', 'first-page': '577', 'article-title': 'Integrating conflicting chemotactic signals', 'volume': '147', 'author': 'Foxman', 'year': '1999', 'journal-title': 'The role of memory in leukocyte navigation. J. Cell Biol.'} / The role of memory in leukocyte navigation. J. Cell Biol. / Integrating conflicting chemotactic signals by Foxman (1999)
  12. 10.1002/(SICI)1521-4141(199907)29:07<2280::AID-IMMU2280>3.0.CO;2-C / Eur. J. Immunol. / Hypoxia inhibits macrophage migration by Turner (1999)
  13. 10.1111/j.1749-6632.1997.tb46238.x / Ann. NY Acad. Sci. / Phagocyte chemoattractant receptors by Boulay (1997)
  14. 10.1016/S0092-8674(00)81784-5 / Cell / G protein signaling events are activated at the leading edge of chemotactic cells by Parent (1998)
  15. 10.1126/science.287.5455.1046 / Science / Roles of PLC-β2 and -β3 and PI3Kγ in chemoattractant-mediated signal transduction by Li (2000)
  16. 10.1126/science.287.5455.1040 / Science / Function of PI3Kg in thymocyte development, T cell activation, and neutrophil migration by Sasaki (2000)
  17. 10.1126/science.287.5455.1049 / Science / Central role for G protein-coupled phosphoinositide 3-kinase γ in inflammation by Hirsch (2000)
  18. 10.1126/science.287.5455.1037 / Science / Polarization of chemoattractant receptor signaling during neutrophil chemotaxis by Servant (2000)
  19. 10.1126/science.287.5455.1034 / Science / Localization of the G protein bg complex in living cells during chemotaxis by Jin (2000)
  20. 10.1006/excr.1999.4701 / Exp. Cell Res. / Signaling by distinct classes of phosphoinositide 3-kinase by Vanhaesebroeck (1999)
  21. 10.1016/S0021-9258(18)82183-4 / J. Biol. Chem. / Specific interactions of chemoattractant factor receptors with G-proteins by Amatruda (1993)
  22. 10.1038/365403a0 / Nature / New roles for G-protein beta gammadimers in transmembrane signaling by Clapham (1993)
  23. {'key': '2023033020111270500_cit-B23', 'first-page': '19080', 'article-title': 'Activation of Akt/protein kinase B by G protein-coupled receptors. A role for alpha and beta gamma subunits of heterotrimeric G proteins acting through phosphatidylinositol-3-OH kinasegamma. J. Biol', 'volume': '273', 'author': 'Murga', 'year': '1998', 'journal-title': 'Chem.'} / Chem. / Activation of Akt/protein kinase B by G protein-coupled receptors. A role for alpha and beta gamma subunits of heterotrimeric G proteins acting through phosphatidylinositol-3-OH kinasegamma. J. Biol by Murga (1998)
  24. 10.1073/pnas.94.26.14489 / Proc. Natl. Acad. Sci. USA / Receptors induce chemotaxis by releasing the betagamma subunit of Gi, not by activating Gq or Gs by Neptune (1997)
  25. 10.1126/science.284.5415.765 / Science / A cell's sense of direction by Parent (1999)
  26. 10.1016/S0959-437X(97)80113-X / Curr. Opin. Genet. Dev. / Novel mechanisms of RTK signal generation by Weiss (1997)
  27. 10.1002/jlb.62.2.145 / J. Leukoc. Biol. / CSF-1 signal transduction by Hamilton (1997)
  28. 10.1002/(SICI)1098-2795(199701)46:1<4::AID-MRD2>3.0.CO;2-V / Mol. Reprod. Dev. / Biology and action of colony-stimulating factor-1 by Stanley (1997)
  29. 10.1002/jcp.1041300316 / J. Cell. Physiol. / Isolation and characterization of a cloned growth factor dependent macrophage cell line, BAC1.2F5 by Morgan (1987)
  30. 10.1242/jcs.93.3.447 / J. Cell Sci. / Colony-stimulating factor-1 induces rapid behavioural responses in the mouse macrophage cell line, BAC1.2FS by Boocock (1989)
  31. 10.1242/jcs.109.4.793 / J. Cell Sci. / Direct observation and quantification of macrophage chemoattraction to the growth factor CSF-1 by Webb (1996)
  32. 10.1002/(SICI)1098-2795(199701)46:1<71::AID-MRD11>3.0.CO;2-6 / Mol. Reprod. Dev. / CSF-1 and its receptor in breast carcinomas and neoplasms of the female reproductive tract by Kacinski (1997)
  33. 10.1042/bj3200069 / Biochem. J. / Association between phosphatidylinositol-3 kinase, Cbl and other tyrosine phosphorylated proteins in colony-stimulating factor-1-stimulated macrophages by Kanagasundaram (1996)
  34. 10.1016/S0962-8924(00)01741-4 / Trends Cell Biol. / Why cytoplasmic signaling proteins should be recruited to cell membranes by Kholodenko (2000)
  35. 10.1074/jbc.270.18.10380 / J. Biol. Chem. / Monocyte colony-stimulating factor stimulates binding of phosphatidylinositol 3-kinase to Grb2.Sos complexes in human monocytes by Saleem (1995)
  36. 10.1038/9045 / Nat. Cell Biol. / Distinct PI(3)Ks mediate mitogenic signaling and cell migration in macrophages by Vanhaesebroeck (1999)
  37. 10.1002/bies.950180109 / BioEssays / The pleckstrin homology domain: an intriguing multifunctional protein module by Shaw (1996)
  38. 10.1016/S0005-2760(98)00141-6 / Biochim. Biophys. Acta / Phospholipid-binding protein domains by Bottomley (1998)
  39. 10.1083/jcb.138.4.913 / J. Cell Biol. / Role of actin polymerization and adhesion to extracellular matrix in Rac- and Rho-induced cytoskeletal reorganization by Machesky (1997)
  40. 10.1016/S0955-0674(99)80011-8 / Curr. Opin. Cell Biol. / Effectors for the Rho GTPases by Aspenstrom (1999)
  41. 10.1016/0092-8674(92)90163-7 / Cell / The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors by Ridley (1992)
  42. 10.1016/S0960-9822(95)00140-0 / Curr. Biol. / Rac and Bcr regulate phagocytic phoxes by Ridley (1995)
  43. 10.1146/annurev.cellbio.12.1.463 / Annu. Rev. Cell Biol. / Focal adhesions, contractility, and signaling by Burridge (1996)
  44. 10.1016/0092-8674(95)90370-4 / Cell / Rho, Rac, and Cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia by Nobes (1995)
  45. 10.1016/0092-8674(92)90164-8 / Cell / The small GTP-binding protein Rac regulates growth factor-induced membrane ruffling by Ridley (1992)
  46. 10.1007/978-3-642-58591-3_4 / Prog. Mol. Subcell. Biol. / The DH protein family, exchange factors for Rho-like GTPases by Stam (1999)
  47. 10.1126/science.279.5350.558 / Science / Role of substrates and products of PI3-kinase in regulating activation of Rac-related guanosine triphosphatases by Vav by Han (1998)
  48. 10.1038/385169a0 / Nature / Phosphotyrosine-dependent activation of Rac-1 GDP/GTP exchange by the vav proto-oncogene product by Crespo (1997)
  49. 10.1146/annurev.cb.10.110194.000335 / Annu. Rev. Cell Biol. / Small GTP-binding proteins and the regulation of the actin cytoskeleton by Hall (1994)
  50. 10.1007/978-3-642-58591-3_5 / Prog. Mol. Subcell. Biol. / RhoGAPs and RhoGDIs, (His)stories of two families by Zalcman (1999)
  51. 10.1016/S0014-5793(98)00020-9 / FEBS Lett. / Differential properties of D4/LyGDI versus RhoGDI: phosphorylation and rho GTPase selectivity by Gorvel (1998)
  52. 10.1083/jcb.135.1.37 / Cell Biol. / Regulation mechanism of ERM (ezrin/radixin/moesin) protein/plasma membrane association: possible involvement of phosphatidylinositol turnover and rho-dependent signaling pathway. J by Hirao (1996)
  53. 10.1038/sj.onc.1201874 / Oncogene / Interaction of radixin with Rho small G protein GDP/GTP exchange protein Dbl by Takahashi (1998)
  54. 10.1074/jbc.274.19.13198 / J. Biol. Chem. / Characterization of rac and cdc42 activation in chemoattractant-stimulated human neutrophils using a novel assay for active GTPases by Benard (1999)
  55. 10.1016/S0960-9822(95)00080-7 / Curr. Biol. / PDGF stimulates an increase in GTP-Rac via activation of phosphoinositide 3-kinase by Hawkins (1995)
  56. 10.1128/MCB.18.8.4744 / Mol. Cell. Biol. / Cytoskeletal reorganization by G protein-coupled receptors is dependent on phosphoinositide 3-kinase gamma, a Rac guanosine exchange factor, and Rac by Ma (1998)
  57. 10.1074/jbc.272.35.22059 / J. Biol. Chem. / A comparative analysis of the phosphoinositide binding specificity of pleckstrin homology domains by Rameh (1997)
  58. 10.1016/S0960-9822(02)70786-0 / Curr. Biol. / Faciogenital dysplasia protein (FGD1) and Vav, two related proteins required for normal embryonic development, are upstream regulators of Rho GTPases by Olson (1996)
  59. {'key': '2023033020111270500_cit-B59', 'first-page': '25204', 'article-title': 'A tyrosine kinase signaling pathway accounts for the majority of phosphatidylinositol 3,4,5-trisphosphate formation in chemoattractant-stimulated human neutrophils. J. Biol', 'volume': '271', 'author': 'Ptasznik', 'year': '1996', 'journal-title': 'Chem.'} / Chem. / A tyrosine kinase signaling pathway accounts for the majority of phosphatidylinositol 3,4,5-trisphosphate formation in chemoattractant-stimulated human neutrophils. J. Biol by Ptasznik (1996)
  60. 10.1074/jbc.274.25.17901 / J. Biol. Chem. / Differential involvement of Galpha12 and Galpha13 in receptor-mediated stress fiber formation by Gohla (1999)
  61. 10.1126/science.280.5372.2112 / Science / Direct stimulation of the guanine nucleotide exchange activity of p115 RhoGEF by Galpha13 by Hart (1998)
  62. 10.1006/excr.1999.4674 / Exp. Cell Res. / Signaling to Rho GTPases by Kjoller (1999)
  63. 10.1126/science.279.5350.509 / Science / Rho GTPases and the actin cytoskeleton by Hall (1998)
  64. 10.1007/978-3-642-58591-3_1 / Prog. Mol. Subcell. Biol. / Rho family proteins and regulation of the actin cytoskeleton by Ridley (1999)
  65. 10.1016/S0955-0674(97)80156-1 / Curr. Opin. Cell Biol. / Rho, Rac and Cdc42 GTPases regulate the organization of the actin cytoskeleton by Tapon (1997)
  66. {'key': '2023033020111270500_cit-B66', 'first-page': '4869', 'article-title': 'The Ras GTPase-activating-protein-related human protein IQGAP2 harbors a potential actin binding domain and interacts with calmodulin and Rho family GTPases. Mol. Cell', 'volume': '16', 'author': 'Brill', 'year': '1996', 'journal-title': 'Biol.'} / Biol. / The Ras GTPase-activating-protein-related human protein IQGAP2 harbors a potential actin binding domain and interacts with calmodulin and Rho family GTPases. Mol. Cell by Brill (1996)
  67. 10.1083/jcb.138.2.363 / J. Cell Biol. / Regulation of actin polymerization in cell-free systems by GTP-gammaS and Cdc42 by Zigmond (1997)
  68. 10.1016/S0960-9822(06)00219-3 / Curr. Biol. / A Cdc42 target protein with homology to the non-kinase domain of FER has a potential role in regulating the actin cytoskeleton by Aspenstrom (1997)
  69. 10.1007/978-3-642-58591-3_2 / Prog. Mol. Subcell. Biol. / Regulation of cytoskeleton and cell adhesion by Rho targets by Kaibuchi (1999)
  70. 10.1073/pnas.94.4.1092 / Proc. Natl. Acad. Sci. USA / p21-activated kinase has substrate specificity similar to Acanthamoeba myosin 1 heavy chain kinase and activates Acanthamoeba myosin 1 by Brzeska (1997)
  71. 10.1093/emboj/17.22.6527 / EMBO J. / PAK4, a novel effector for Cdc42Hs, is implicated in the reorganization of the actin cytoskeleton and in the formation of filopodia by Abo (1998)
  72. 10.1007/978-3-642-58591-3_6 / Prog. Mol. Subcell. Biol. / Roles of PAK family kinases by Manser (1999)
  73. 10.1093/emboj/16.11.3044 / EMBO J. / p140mDia, a mammalian homolog of Drosophila diaphanous, is a target protein for Rho small GTPase and is a ligand for profilin by Watanabe (1997)
  74. 10.1007/s000180050242 / Cell. Mol. Life Sci. / Understanding the molecular basis of Wiskott-Aldrich syndrome by Abo (1998)
  75. 10.1016/S1357-2725(98)00118-6 / Int. J. Biochem. Cell Biol. / Wiskott-Aldrich syndrome protein, WASP by O'Sullivan (1999)
  76. 10.1097/00062752-199901000-00003 / Curr. Opin. Hematol. / Recent advances in our understanding of Wiskott-Aldrich syndrome by Sullivan (1999)
  77. 10.1016/S0960-9822(02)00423-2 / Curr. Biol. / Two GTPases, cdc42 and rac, bind directly to a protein implicated in the immunodeficiency disorder Wiskott-Aldrich syndrome by Aspenstrom (1996)
  78. 10.1073/pnas.93.11.5615 / Proc. Natl. Acad. Sci. USA / Direct interaction of the Wiskott-Aldrich syndrome protein with the GTPase Cdc42 by Kolluri (1996)
  79. 10.1016/S0092-8674(00)81050-8 / Cell / Wiskott-Aldrich syndrome protein, a novel effector for the GTPase CDC42Hs, is implicated in actin polymerization by Symons (1996)
  80. 10.1016/S0960-9822(99)80161-4 / Curr. Biol. / Inducible recruitment of Cdc42 or WASP to a cell-surface receptor triggers actin polymerization and filopodium formation by Castellano (1999)
  81. 10.1146/annurev.immunol.17.1.905 / Annu. Rev. Immunol. / The Wiskott-Aldrich syndrome protein (WASP): roles in signaling and cytoskeletal organization by Snapper (1999)
  82. 10.1016/S0092-8674(00)80757-6 / Cell / Structure of the enabled/VASP homology 1 domain-peptide complex: a key component in the spatial control of actin assembly by Prehoda (1999)
  83. 10.1016/S0962-8924(98)01411-1 / Trends Cell Biol. / Waltzing with WASP by Ramesh (1999)
  84. 10.1093/emboj/17.22.6516 / EMBO J. / The essential role of profilin in the assembly of actin for microspike formation by Suetsugu (1998)
  85. 10.1016/S0960-9822(98)00015-3 / Curr. Biol. / Scar1 and the related Wiskott-Aldrich syndrome protein, WASP, regulate the actin cytoskeleton through the Arp2/3 complex by Machesky (1998)
  86. 10.1016/S0960-9822(99)80337-6 / Curr. Biol. / The Arp2/3 complex is essential for the actin-based motility of Listeria monocytogenes by May (1999)
  87. 10.1042/bj3280105 / Biochem. J. / Mammalian actin-related protein 2/3 complex localizes to regions of lamellipodial protrusion and is composed of evolutionarily conserved proteins by Machesky (1997)
  88. 10.1073/pnas.95.11.6181 / Proc. Natl. Acad. Sci. USA / The interaction of Arp2/3 complex with actin: nucleation, high affinity pointed end capping, and formation of branching networks of filaments by Mullins (1998)
  89. 10.1016/S0959-440X(99)80034-7 / Curr. Opin. Struct. Biol. / Structure and function of the Arp2/3 complex by Mullins (1999)
  90. 10.4049/jimmunol.162.2.837 / J. Immunol. / Multiple signal transduction pathways regulate TNF-induced actin reorganization in macrophages: inhibition of Cdc42-mediated filopodium formation by TNF by Peppelenbosch (1999)
  91. 10.1038/385537a0 / Nature / Integrin-ligand binding properties govern cell migration speed through cell-substratum adhesiveness by Palecek (1997)
  92. 10.1093/emboj/17.15.4391 / EMBO J. / A beta1 integrin signaling pathway involving Src-family kinases, Cbl and PI-3 kinase is required for macrophage spreading and migration by Meng (1998)
  93. 10.1002/jlb.65.3.313 / J. Leukoc. Biol. / Integrin signal transduction in myeloid leukocytes by Lowell (1999)
  94. 10.1038/33340 / Nature / Chemokines and leukocyte traffic by Baggiolini (1998)
  95. 10.1038/32588 / Nature / Dendritic cells and the control of immunity by Banchereau (1998)
  96. {'key': '2023033020111270500_cit-B96', 'first-page': '537', 'article-title': 'Is Wiskott-Aldrich syndrome a cell trafficking disorder? Immunol', 'volume': '19', 'author': 'Thrasher', 'year': '1998', 'journal-title': 'Today'} / Today / Is Wiskott-Aldrich syndrome a cell trafficking disorder? Immunol by Thrasher (1998)
  97. 10.1046/j.1365-2141.1998.00767.x / Br. J. Haematol. / Chemotaxis of macrophages is abolished in the Wiskott-Aldrich syndrome by Zicha (1998)
  98. 10.4049/jimmunol.161.2.1026 / Immunol. / Monocytes from Wiskott-Aldrich patients display reduced chemotaxis and lack of cell polarization in response to monocyte chemoattractant protein-1 and formyl-methionyl-leucyl-phenylalanine. J by Badolato (1998)
  99. 10.1073/pnas.92.11.5027 / Proc. Natl. Acad. Sci. USA / Regulation of the polarization of T cells towards antigen-presenting cells by Ras-related GTPase Cdc42 by Stowers (1995)
  100. 10.1002/(SICI)1521-4141(199810)28:10<3259::AID-IMMU3259>3.0.CO;2-B / Eur. J. Immunol. / Intrinsic dendritic cell abnormalities in Wiskott-Aldrich syndrome by Binks (1998)
  101. 10.1101/gad.12.11.1610 / Genes Dev. / Targeted disruption of SHIP leads to hemopoietic perturbations, lung pathology, and a shortened life span by Helgason (1998)
  102. 10.1083/jcb.99.4.1461 / J. Cell Biol. / Asymmetric distribution of the chemotactic peptide receptor on polymorphonuclear leukocytes by Sullivan (1984)
  103. 10.1091/mbc.10.4.1163 / Mol. Biol. Cell / Dynamics of a chemoattractant receptor in living neutrophils during chemotaxis by Servant (1999)
  104. 10.1007/s000180050374 / Cell Mol. Life Sci. / Molecular basis of localized responses during chemotaxis in amoebae and leukocytes by van Es (1999)
  105. 10.1002/j.1460-2075.1991.tb07948.x / EMBO J. / Role of dimerization and modification of the CSF-1 receptor in its activation and internalization during the CSF-1 response by Li (1991)
  106. 10.1007/BF01204345 / Biosci. Rep. / Endosomes, receptor tyrosine kinase internalization and signal transduction by Bergeron (1995)
  107. 10.1038/10042 / Nat. Cell Biol. / Spatial control of actin polymerization during neutrophil chemotaxis by Weiner (1999)
  108. 10.1016/S0092-8674(00)81278-7 / Cell / Origins of cell polarity by Drubin (1996)
Dates
Type When
Created 2 years, 11 months ago (Sept. 27, 2022, 9:38 p.m.)
Deposited 1 year, 9 months ago (Nov. 27, 2023, 4:54 p.m.)
Indexed 5 months ago (March 29, 2025, 1:04 p.m.)
Issued 24 years, 9 months ago (Nov. 1, 2000)
Published 24 years, 9 months ago (Nov. 1, 2000)
Published Online 24 years, 9 months ago (Nov. 1, 2000)
Published Print 24 years, 9 months ago (Nov. 1, 2000)
Funders 0

None

@article{Jones_2000, title={Cellular signaling in macrophage migration and chemotaxis}, volume={68}, ISSN={0741-5400}, url={http://dx.doi.org/10.1189/jlb.68.5.593}, DOI={10.1189/jlb.68.5.593}, number={5}, journal={Journal of Leukocyte Biology}, publisher={Oxford University Press (OUP)}, author={Jones, Gareth E}, year={2000}, month=nov, pages={593–602} }