Although directed migration of eukaryotic cells may have evolved to escape nutrient depletion, it has been adopted for an extensive range of physiological events during development and in the adult organism. The subversion of these movements results in disease, such as cancer. Mechanisms of propulsion and sensing are extremely diverse, but most eukaryotic cells move by extending actin-filled protrusions termed macropinosomes, pseudopodia, or lamellipodia or by extension of blebs. In addition to motility, directed migration involves polarity and directional sensing. The hundreds of gene products involved in these processes are organized into networks of parallel and interconnected pathways. Many of these components are activated or inhibited coordinately with stimulation and on each spontaneously extended protrusion. Moreover, these networks display hallmarks of excitability, including all-or-nothing responsiveness and wave propagation. Cellular protrusions result from signal transduction waves that propagate outwardly from an origin and drive cytoskeletal activity. The range of the propagating waves and hence the size of the protrusions can be altered by lowering or raising the threshold for network activation, with larger and wider protrusions favoring gliding or oscillatory behavior over amoeboid migration. Here, we evaluate the variety of models of excitable networks controlling directed migration and outline critical tests. We also discuss the utility of this emerging view in producing cell migration and in integrating the various extrinsic cues that direct migration.

[Erratum, Closure]

An erratum has been published for this article:
Erratum: Excitable Signal Transduction Networks in Directed Cell Migration

Article metrics loading...

Loading full text...

Full text loading...


Literature Cited

  1. Allen GM, Mogilner A, Theriot JA. 2013. Electrophoresis of cellular membrane components creates the directional cue guiding keratocyte galvanotaxis. Curr. Biol. 23:560–68 [Google Scholar]
  2. Anderson KI, Cross R. 2000. Contact dynamics during keratocyte motility. Curr. Biol. 10:253–60 [Google Scholar]
  3. Arai Y, Shibata T, Matsuoka S, Sato MJ, Yanagida T, Ueda M. 2010. Self-organization of the phosphatidylinositol lipids signaling system for random cell migration. PNAS 107:12399–404 [Google Scholar]
  4. Armitage JP, Hellingwerf KJ. 2003. Light-induced behavioral responses (‘phototaxis’) in prokaryotes. Photosynth. Res. 76:145–55 [Google Scholar]
  5. Artemenko Y, Axiotakis L, Borleis J, Iglesias PA, Devreotes PN. 2016. Chemical and mechanical stimuli act on common signal transduction and cytoskeletal networks. PNAS 113:E7500–9 [Google Scholar]
  6. Artemenko Y, Batsios P, Borleis J, Gagnon Z, Lee J. et al. 2012. Tumor suppressor Hippo/MST1 kinase mediates chemotaxis by regulating spreading and adhesion. PNAS 109:13632–37 [Google Scholar]
  7. Artemenko Y, Lampert TJ, Devreotes PN. 2014. Moving towards a paradigm: common mechanisms of chemotactic signaling in Dictyostelium and mammalian leukocytes. Cell. Mol. Life Sci. 71:3711–47 [Google Scholar]
  8. Bagorda A, Parent CA. 2008. Eukaryotic chemotaxis at a glance. J. Cell Sci. 121:2621–24 [Google Scholar]
  9. Barnhart EL, Allen GM, Jülicher F, Theriot JA. 2010. Bipedal locomotion in crawling cells. Biophys. J. 98:933–42 [Google Scholar]
  10. Baumann K. 2014. Stem cells: moving out of the niche. Nat. Rev. Mol. Cell Biol. 15:79 [Google Scholar]
  11. Blaser H, Reichman-Fried M, Castanon I, Dumstrei K, Marlow FL. et al. 2006. Migration of zebrafish primordial germ cells: a role for myosin contraction and cytoplasmic flow. Dev. Cell 11:613–27 [Google Scholar]
  12. Bloomfield G, Traynor D, Sander SP, Veltman DM, Pachebat JA, Kay RR. 2015. Neurofibromin controls macropinocytosis and phagocytosis in Dictyostelium. eLife 4:e04940 [Google Scholar]
  13. Bosgraaf L, van Haastert PJ. 2006. The regulation of myosin II in Dictyostelium. Eur. J. Cell Biol. 85:969–79 [Google Scholar]
  14. Bosgraaf L, Van Haastert PJ. 2009. The ordered extension of pseudopodia by amoeboid cells in the absence of external cues. PLOS ONE 4:e5253 [Google Scholar]
  15. Bretschneider T, Anderson K, Ecke M, Müller-Taubenberger A, Schroth-Diez B. et al. 2009. The three-dimensional dynamics of actin waves, a model of cytoskeletal self-organization. Biophys. J. 96:2888–900 [Google Scholar]
  16. Bretschneider T, Diez S, Anderson K, Heuser J, Clarke M. et al. 2004. Dynamic actin patterns and Arp2/3 assembly at the substrate-attached surface of motile cells. Curr. Biol. 14:1–10 [Google Scholar]
  17. Case LB, Waterman CM. 2011. Adhesive F-actin waves: a novel integrin-mediated adhesion complex coupled to ventral actin polymerization. PLOS ONE 6:e26631 [Google Scholar]
  18. Caterina MJ, Devreotes PN. 1991. Molecular insights into eukaryotic chemotaxis. FASEB J 5:3078–85 [Google Scholar]
  19. Charest PG, Shen Z, Lakoduk A, Sasaki AT, Briggs SP, Firtel RA. 2010. A Ras signaling complex controls the RasC-TORC2 pathway and directed cell migration. Dev. Cell 18:737–49 [Google Scholar]
  20. Chen BC, Legant WR, Wang K, Shao L, Milkie DE. et al. 2014. Lattice light-sheet microscopy: imaging molecules to embryos at high spatiotemporal resolution. Science 346:1257998 [Google Scholar]
  21. Chen L, Iijima M, Tang M, Landree MA, Huang YE. et al. 2007. PLA2 and PI3K/PTEN pathways act in parallel to mediate chemotaxis. Dev. Cell 12:603–14 [Google Scholar]
  22. Chen L, Janetopoulos C, Huang YE, Iijima M, Borleis J, Devreotes PN. 2003. Two phases of actin polymerization display different dependencies on PI(3,4,5)P3 accumulation and have unique roles during chemotaxis. Mol. Biol. Cell 14:5028–37 [Google Scholar]
  23. Condeelis J, Bresnick A, Demma M, Dharmawardhane S, Eddy R. et al. 1990. Mechanisms of amoeboid chemotaxis: an evaluation of the cortical expansion model. Dev. Genet. 11:333–40 [Google Scholar]
  24. Condeelis J, Singer RH, Segall JE. 2005. The great escape: when cancer cells hijack the genes for chemotaxis and motility. Annu. Rev. Cell Dev. Biol. 21:695–718 [Google Scholar]
  25. Cooper RM, Wingreen NS, Cox EC. 2012. An excitable cortex and memory model successfully predicts new pseudopod dynamics. PLOS ONE 7:e33528 [Google Scholar]
  26. Cortese B, Palamà IE, D'Amone S, Gigli G. 2014. Influence of electrotaxis on cell behaviour. Integr. Biol. 6:817–30 [Google Scholar]
  27. Décave E, Rieu D, Dalous J, Fache S, Brechet Y. et al. 2003. Shear flow-induced motility of Dictyostelium discoideum cells on solid substrate. J. Cell Sci. 116:4331–43 [Google Scholar]
  28. Diz-Muñoz A, Fletcher DA, Weiner OD. 2013. Use the force: membrane tension as an organizer of cell shape and motility. Trends Cell Biol 23:47–53 [Google Scholar]
  29. Diz-Muñoz A, Thurley K, Chintamen S, Altschuler SJ, Wu LF. et al. 2016. Membrane tension acts through PLD2 and mTORC2 to limit actin network assembly during neutrophil migration. PLOS Biol 14:e1002474 [Google Scholar]
  30. Ecke M, Gerisch G. 2017. Co-existence of Ras activation in a chemotactic signal transduction pathway and in an autonomous wave-forming system. Small GTPases 2017:1–9 [Google Scholar]
  31. Fackler OT, Grosse R. 2008. Cell motility through plasma membrane blebbing. J. Cell Biol. 181:879–84 [Google Scholar]
  32. Ferguson GJ, Milne L, Kulkarni S, Sasaki T, Walker S. et al. 2007. PI3Kγ has an important context-dependent role in neutrophil chemokinesis. Nat. Cell Biol. 9:86–91 [Google Scholar]
  33. Filić V, Marinović M, Faix J, Weber I. 2012. A dual role for Rac1 GTPases in the regulation of cell motility. J. Cell Sci. 125:387–98 [Google Scholar]
  34. Funamoto S, Meili R, Lee S, Parry L, Firtel RA. 2002. Spatial and temporal regulation of 3-phosphoinositides by PI 3-kinase and PTEN mediates chemotaxis. Cell 109:611–23 [Google Scholar]
  35. Futrelle RP, Traut J, McKee WG. 1982. Cell behavior in Dictyostelium discoideum: preaggregation response to localized cyclic AMP pulses. J. Cell Biol. 92:807–21 [Google Scholar]
  36. Gao RC, Zhang XD, Sun YH, Kamimura Y, Mogilner A. et al. 2011. Different roles of membrane potentials in electrotaxis and chemotaxis of Dictyostelium cells. Eukaryot. Cell 10:1251–56 [Google Scholar]
  37. Gerisch G. 2010. Self-organizing actin waves that simulate phagocytic cup structures. PMC Biophys 3:7 [Google Scholar]
  38. Gerisch G. 2011. Actin switches in phagocytosis. Commun. Integr. Biol. 4:344–45 [Google Scholar]
  39. Gerisch G, Ecke M, Schroth-Diez B, Gerwig S, Engel U. et al. 2009. Self-organizing actin waves as planar phagocytic cup structures. Cell Adhes. Migr. 3:373–82 [Google Scholar]
  40. Gerisch G, Ecke M, Wischnewski D, Schroth-Diez B. 2011. Different modes of state transitions determine pattern in the Phosphatidylinositide-Actin system. BMC Cell Biol 12:42 [Google Scholar]
  41. Gerisch G, Hess B. 1974. Cyclic-AMP-controlled oscillations in suspended Dictyostelium cells: their relation to morphogenetic cell interactions. PNAS 71:2118–22 [Google Scholar]
  42. Gupton SL, Waterman-Storer CM. 2006. Spatiotemporal feedback between actomyosin and focal-adhesion systems optimizes rapid cell migration. Cell 125:1361–74 [Google Scholar]
  43. Haeger A, Wolf K, Zegers MM, Friedl P. 2015. Collective cell migration: guidance principles and hierarchies. Trends Cell Biol 25:556–66 [Google Scholar]
  44. Harland B, Walcott S, Sun SX. 2011. Adhesion dynamics and durotaxis in migrating cells. Phys. Biol. 8:015011 [Google Scholar]
  45. Haugh JM, Huang AC, Wiley HS, Wells A, Lauffenburger DA. 1999. Internalized epidermal growth factor receptors participate in the activation of p21ras in fibroblasts. J. Biol. Chem. 274:34350–60 [Google Scholar]
  46. Hecht I, Skoge ML, Charest PG, Ben-Jacob E, Firtel RA. et al. 2011. Activated membrane patches guide chemotactic cell motility. PLOS Comput. Biol. 7:e1002044 [Google Scholar]
  47. Hoeller O, Kay RR. 2007. Chemotaxis in the absence of PIP3 gradients. Curr. Biol. 17:813–17 [Google Scholar]
  48. Hoeller O, Toettcher JE, Cai H, Sun Y, Huang CH. et al. 2016. Gβ regulates coupling between actin oscillators for cell polarity and directional migration. PLOS Biol 14:e1002381 [Google Scholar]
  49. Hou Y, Hedberg S, Schneider IC. 2012. Differences in adhesion and protrusion properties correlate with differences in migration speed under EGF stimulation. BMC Biophys 5:8 [Google Scholar]
  50. Houk AR, Jilkine A, Mejean CO, Boltyanskiy R, Dufresne ER. et al. 2012. Membrane tension maintains cell polarity by confining signals to the leading edge during neutrophil migration. Cell 148:175–88 [Google Scholar]
  51. Huang CH, Tang M, Shi C, Iglesias PA, Devreotes PN. 2013. An excitable signal integrator couples to an idling cytoskeletal oscillator to drive cell migration. Nat. Cell Biol. 15:1307–16 [Google Scholar]
  52. Iijima M, Devreotes P. 2002. Tumor suppressor PTEN mediates sensing of chemoattractant gradients. Cell 109:599–610 [Google Scholar]
  53. Inoue T, Meyer T. 2008. Synthetic activation of endogenous PI3K and Rac identifies an AND-gate switch for cell polarization and migration. PLOS ONE 3:e3068 [Google Scholar]
  54. Insall RH. 2010. Understanding eukaryotic chemotaxis: a pseudopod-centred view. Nat. Rev. Mol. Cell Biol. 11:453–58 [Google Scholar]
  55. Janetopoulos C, Ma L, Devreotes PN, Iglesias PA. 2004. Chemoattractant-induced phosphatidylinositol 3,4,5-trisphosphate accumulation is spatially amplified and adapts, independent of the actin cytoskeleton. PNAS 101:8951–56 [Google Scholar]
  56. Jasnin M, Ecke M, Baumeister W, Gerisch G. 2016. Actin organization in cells responding to a perforated surface, revealed by live imaging and cryo-electron tomography. Structure 24:1031–43 [Google Scholar]
  57. Jin T, Xu X, Hereld D. 2008. Chemotaxis, chemokine receptors and human disease. Cytokine 44:1–8 [Google Scholar]
  58. Jin T, Zhang N, Long Y, Parent CA, Devreotes PN. 2000. Localization of the G protein betagamma complex in living cells during chemotaxis. Science 287:1034–36 [Google Scholar]
  59. Kabacoff C, Xiong Y, Musib R, Reichl EM, Kim J. et al. 2007. Dynacortin facilitates polarization of chemotaxing cells. BMC Biol 5:53 [Google Scholar]
  60. Kakumoto T, Nakata T. 2013. Optogenetic control of PIP3: PIP3 is sufficient to induce the actin-based active part of growth cones and is regulated via endocytosis. PLOS ONE 8:e70861 [Google Scholar]
  61. Kamimura Y, Xiong Y, Iglesias PA, Hoeller O, Bolourani P, Devreotes PN. 2008. PIP3-independent activation of TorC2 and PKB at the cell's leading edge mediates chemotaxis. Curr. Biol. 18:1034–43 [Google Scholar]
  62. Kaur H, Park CS, Lewis JM, Haugh JM. 2006. Quantitative model of Ras–phosphoinositide 3-kinase signalling cross-talk based on co-operative molecular assembly. Biochem. J. 393:235–43 [Google Scholar]
  63. Keller R. 2005. Cell migration during gastrulation. Curr. Opin. Cell Biol. 17:533–41 [Google Scholar]
  64. Keren K, Theriot JA. 2008. Biophysical aspects of actin-based cell motility in fish epithelial keratocytes. Cell Motility P Lenz 31–58 New York: Springer [Google Scholar]
  65. Khanna A, Lotfi P, Chavan AJ, Montaño NM, Bolourani P. et al. 2016. The small GTPases Ras and Rap1 bind to and control TORC2 activity. Sci. Rep. 6:25823 [Google Scholar]
  66. Klämbt C. 2009. Modes and regulation of glial migration in vertebrates and invertebrates. Nat. Rev. Neurosci. 10:769–79 [Google Scholar]
  67. Lakshman R, Finn A. 2001. Neutrophil disorders and their management. J. Clin. Pathol. 54:7–19 [Google Scholar]
  68. Lampert T, Kamprad N, Edwards M, Borelis J, Watson A. et al. 2017. Shear force–based genetic screen reveals negative regulators of cell adhesion and protrusive activity. PNAS In press [Google Scholar]
  69. Langridge PD, Kay RR. 2006. Blebbing of Dictyostelium cells in response to chemoattractant. Exp. Cell Res. 312:2009–17 [Google Scholar]
  70. Leptin M. 2005. Gastrulation movements: the logic and the nuts and bolts. Dev. Cell 8:305–20 [Google Scholar]
  71. Levchenko A, Iglesias PA. 2002. Models of eukaryotic gradient sensing: application to chemotaxis of amoebae and neutrophils. Biophys. J. 82:50–63 [Google Scholar]
  72. Levine H, Kessler DA, Rappel WJ. 2006. Directional sensing in eukaryotic chemotaxis: a balanced inactivation model. PNAS 103:9761–66 [Google Scholar]
  73. Lim CJ, Spiegelman GB, Weeks G. 2002. Cytoskeletal regulation by Dictyostelium Ras subfamily proteins. J. Muscle Res. Cell Motil. 23:729–36 [Google Scholar]
  74. Liu Q, Sasaki T, Kozieradzki I, Wakeham A, Itie A. et al. 1999. SHIP is a negative regulator of growth factor receptor–mediated PKB/Akt activation and myeloid cell survival. Genes Dev 13:786–91 [Google Scholar]
  75. Lo CM, Wang HB, Dembo M, Wang YL. 2000. Cell movement is guided by the rigidity of the substrate. Biophys. J. 79:144–52 [Google Scholar]
  76. Maniak M. 2001. Fluid-phase uptake and transit in axenic Dictyostelium cells. Biochim. Biophys. Acta 1525:197–204 [Google Scholar]
  77. Meinhardt H. 1999. Orientation of chemotactic cells and growth cones: models and mechanisms. J. Cell Sci. 112:2867–74 [Google Scholar]
  78. Meng X, Arocena M, Penninger J, Gage FH, Zhao M, Song B. 2011. PI3K mediated electrotaxis of embryonic and adult neural progenitor cells in the presence of growth factors. Exp. Neurol. 227:210–17 [Google Scholar]
  79. Miao Y, Bhattacharya S, Edwards M, Cai H, Inoue T. et al. 2017. Altering the threshold of an excitable signal transduction network changes cell migratory modes. Nat. Cell Biol. 19:329–40 [Google Scholar]
  80. Mogilner A, Keren K. 2009. The shape of motile cells. Curr. Biol. 19:R762–71 [Google Scholar]
  81. Montell DJ. 2008. Morphogenetic cell movements: diversity from modular mechanical properties. Science 322:1502–5 [Google Scholar]
  82. Moulding DA, Record J, Malinova D, Thrasher AJ. 2013. Actin cytoskeletal defects in immunodeficiency. Immunol. Rev. 256:282–99 [Google Scholar]
  83. Neilson MP, Veltman DM, van Haastert PJ, Webb SD, Mackenzie JA, Insall RH. 2011. Chemotaxis: a feedback-based computational model robustly predicts multiple aspects of real cell behaviour. PLOS Biol 9:e1000618 [Google Scholar]
  84. Neptune ER, Iiri T, Bourne HR. 1999. i is not required for chemotaxis mediated by Gi-coupled receptors. J. Biol. Chem. 274:2824–28 [Google Scholar]
  85. Nishikawa M, Hörning M, Ueda M, Shibata T. 2014. Excitable signal transduction induces both spontaneous and directional cell asymmetries in the phosphatidylinositol lipid signaling system for eukaryotic chemotaxis. Biophys. J. 106:723–34 [Google Scholar]
  86. Nourshargh S, Alon R. 2014. Leukocyte migration into inflamed tissues. Immunity 41:694–707 [Google Scholar]
  87. O'Neill PR, Kalyanaraman V, Gautam N. 2016. Subcellular optogenetic activation of Cdc42 controls local and distal signaling to drive immune cell migration. Mol. Biol. Cell 27:1442–50 [Google Scholar]
  88. Parent CA, Devreotes PN. 1999. A cell's sense of direction. Science 284:765–70 [Google Scholar]
  89. Parsons JT, Horwitz AR, Schwartz MA. 2010. Cell adhesion: integrating cytoskeletal dynamics and cellular tension. Nat. Rev. Mol. Cell Biol. 11:633–43 [Google Scholar]
  90. Petrie RJ, Doyle AD, Yamada KM. 2009. Random versus directionally persistent cell migration. Nat. Rev. Mol. Cell Biol. 10:538–49 [Google Scholar]
  91. Pollitt AY, Blagg SL, Ibarra N, Insall RH. 2006. Cell motility and SCAR localisation in axenically growing Dictyostelium cells. Eur. J. Cell Biol. 85:1091–98 [Google Scholar]
  92. Postma M, Roelofs J, Goedhart J, Gadella TW, Visser AJ, Van Haastert PJ. 2003. Uniform cAMP stimulation of Dictyostelium cells induces localized patches of signal transduction and pseudopodia. Mol. Biol. Cell 14:5019–27 [Google Scholar]
  93. Ramot D, MacInnis BL, Lee HC, Goodman MB. 2008. Thermotaxis is a robust mechanism for thermoregulation in Caenorhabditis elegans nematodes. J. Neurosci. 28:12546–57 [Google Scholar]
  94. Reymond N, d'Água BB, Ridley AJ. 2013. Crossing the endothelial barrier during metastasis. Nat. Rev. Cancer 13:858–70 [Google Scholar]
  95. Richardson BE, Lehmann R. 2010. Mechanisms guiding primordial germ cell migration: strategies from different organisms. Nat. Rev. Mol. Cell Biol. 11:37–49 [Google Scholar]
  96. Rørth P. 2011. Whence directionality: guidance mechanisms in solitary and collective cell migration. Dev. Cell 20:9–18 [Google Scholar]
  97. Ryan GL, Watanabe N, Vavylonis D. 2012. A review of models of fluctuating protrusion and retraction patterns at the leading edge of motile cells. Cytoskeleton 69:195–206 [Google Scholar]
  98. Sarraj B, Massberg S, Li Y, Kasorn A, Subramanian K. et al. 2009. Myeloid-specific deletion of tumor suppressor PTEN augments neutrophil transendothelial migration during inflammation. J. Immunol. 182:7190–200 [Google Scholar]
  99. Sasaki AT, Janetopoulos C, Lee S, Charest PG, Takeda K. et al. 2007. G protein–independent Ras/PI3K/F-actin circuit regulates basic cell motility. J. Cell Biol. 178:185–91 [Google Scholar]
  100. Satulovsky J, Lui R, Wang YL. 2008. Exploring the control circuit of cell migration by mathematical modeling. Biophys. J. 94:3671–83 [Google Scholar]
  101. Schroth-Diez B, Gerwig S, Ecke M, Hegerl R, Diez S, Gerisch G. 2009. Propagating waves separate two states of actin organization in living cells. HFSP J 3:412–27 [Google Scholar]
  102. Shaw TJ, Martin P. 2009. Wound repair at a glance. J. Cell Sci. 122:Pt 183209–13 [Google Scholar]
  103. Shi C, Huang CH, Devreotes PN, Iglesias PA. 2013. Interaction of motility, directional sensing, and polarity modules recreates the behaviors of chemotaxing cells. PLOS Comput. Biol. 9:e1003122 [Google Scholar]
  104. Skoge M, Yue H, Erickstad M, Bae A, Levine H. et al. 2014. Cellular memory in eukaryotic chemotaxis. PNAS 111:14448–53 [Google Scholar]
  105. Swanson JA, Taylor DL. 1982. Local and spatially coordinated movements in Dictyostelium discoideum amoebae during chemotaxis. Cell 28:225–32 [Google Scholar]
  106. Takeda K, Sasaki AT, Ha H, Seung HA, Firtel RA. 2007. Role of phosphatidylinositol 3-kinases in chemotaxis in Dictyostelium. J. Biol. Chem. 282:11874–84 [Google Scholar]
  107. Tang M, Wang M, Shi C, Iglesias PA, Devreotes PN, Huang CH. 2014. Evolutionarily conserved coupling of adaptive and excitable networks mediates eukaryotic chemotaxis. Nat. Commun. 5:5175 [Google Scholar]
  108. Taniguchi D, Ishihara S, Oonuki T, Honda-Kitahara M, Kaneko K, Sawai S. 2013. Phase geometries of two-dimensional excitable waves govern self-organized morphodynamics of amoeboid cells. PNAS 110:5016–21 [Google Scholar]
  109. Tessier-Lavigne M. 1994. Axon guidance by diffusible repellants and attractants. Curr. Opin. Genet. Dev. 4:596–601 [Google Scholar]
  110. Theveneau E, Marchant L, Kuriyama S, Gull M, Moepps B. et al. 2010. Collective chemotaxis requires contact-dependent cell polarity. Dev. Cell 19:39–53 [Google Scholar]
  111. Theveneau E, Mayor R. 2012. Neural crest delamination and migration: from epithelium-to-mesenchyme transition to collective cell migration. Dev. Biol. 366:34–54 [Google Scholar]
  112. Toettcher JE, Gong D, Lim WA, Weiner OD. 2011. Light-based feedback for controlling intracellular signaling dynamics. Nat. Methods 8:837–39 [Google Scholar]
  113. van Haastert PJ, Keizer-Gunnink I, Kortholt A. 2017. Coupled excitable Ras and F-actin activation mediate spontaneous pseudopod formation and directed cell movement. Mol. Biol. Cell 28:922–34 [Google Scholar]
  114. Veeranki S, Kim B, Kim L. 2008. The GPI-anchored superoxide dismutase SodC is essential for regulating basal Ras activity and for chemotaxis of Dictyostelium discoideum. J. Cell Sci. 121:3099–108 [Google Scholar]
  115. Veltman DM, Keizer-Gunnik I, Van Haastert PJ. 2008. Four key signaling pathways mediating chemotaxis in Dictyostelium discoideum. J. Cell Biol. 180:747–53 [Google Scholar]
  116. Veltman DM, Williams TD, Bloomfield G, Chen BC, Betzig E. et al. 2016. A plasma membrane template for macropinocytic cups. eLife 5:e20085 [Google Scholar]
  117. Vicente-Manzanares M, Ma X, Adelstein RS, Horwitz AR. 2009. Non-muscle myosin II takes centre stage in cell adhesion and migration. Nat. Rev. Mol. Cell Biol. 10:778–90 [Google Scholar]
  118. Vicker MG. 1994. The regulation of chemotaxis and chemokinesis in Dictyostelium amoebae by temporal signals and spatial gradients of cyclic AMP. J. Cell Sci. 107:659–67 [Google Scholar]
  119. Vicker MG. 2002. F-actin assembly in Dictyostelium cell locomotion and shape oscillations propagates as a self-organized reaction-diffusion wave. FEBS Lett5105–9 [Google Scholar]
  120. Wang MJ, Artemenko Y, Cai WJ, Iglesias PA, Devreotes PN. 2014. The directional response of chemotactic cells depends on a balance between cytoskeletal architecture and the external gradient. Cell Rep 9:1110–21 [Google Scholar]
  121. Wang Y, Ku CJ, Zhang ER, Artyukhin AB, Weiner OD. et al. 2013. Identifying network motifs that buffer front-to-back signaling in polarized neutrophils. Cell Rep 3:1607–16 [Google Scholar]
  122. Weiger MC, Ahmed S, Welf ES, Haugh JM. 2010. Directional persistence of cell migration coincides with stability of asymmetric intracellular signaling. Biophys. J. 98:67–75 [Google Scholar]
  123. Weiger MC, Parent CA. 2012. Phosphoinositides in chemotaxis. Subcell. Biochem. 59:217–54 [Google Scholar]
  124. Weiner OD, Marganski WA, Wu LF, Altschuler SJ, Kirschner MW. 2007. An actin-based wave generator organizes cell motility. PLOS Biol 5:e221 [Google Scholar]
  125. Weiner OD, Neilsen PO, Prestwich GD, Kirschner MW, Cantley LC, Bourne HR. 2002. A PtdInsP3- and Rho GTPase–mediated positive feedback loop regulates neutrophil polarity. Nat. Cell Biol. 4:509–13 [Google Scholar]
  126. Wen Z, Zheng JQ. 2006. Directional guidance of nerve growth cones. Curr. Opin. Neurobiol. 16:52–58 [Google Scholar]
  127. Weninger W, Biro M, Jain R. 2014. Leukocyte migration in the interstitial space of non-lymphoid organs. Nat. Rev. Immunol. 14:232–46 [Google Scholar]
  128. Whitaker BD, Poff KL. 1980. Thermal adaptation of thermosensing and negative thermotaxis in Dictyostelium. Exp. Cell Res. 128:87–93 [Google Scholar]
  129. Winans AM, Collins SR, Meyer T. 2016. Waves of actin and microtubule polymerization drive microtubule-based transport and neurite growth before single axon formation. eLife 5:e12387 [Google Scholar]
  130. Wolf K, Mazo I, Leung H, Engelke K, von Andrian UH. et al. 2003. Compensation mechanism in tumor cell migration: mesenchymal-amoeboid transition after blocking of pericellular proteolysis. J. Cell Biol. 160:267–77 [Google Scholar]
  131. Wright DE, Wagers AJ, Gulati AP, Johnson FL, Weissman IL. 2001. Physiological migration of hematopoietic stem and progenitor cells. Science 294:1933–36 [Google Scholar]
  132. Wu L, Valkema R, Van Haastert PJ, Devreotes PN. 1995. The G protein beta subunit is essential for multiple responses to chemoattractants in Dictyostelium. J. Cell Biol. 129:1667–75 [Google Scholar]
  133. Wu M, Wu X, De Camilli P. 2013. Calcium oscillations–coupled conversion of actin travelling waves to standing oscillations. PNAS 110:1339–44 [Google Scholar]
  134. Xiong D, Xiao S, Guo S, Lin Q, Nakatsu F, Wu M. 2016. Frequency and amplitude control of cortical oscillations by phosphoinositide waves. Nat. Chem. Biol. 12:159–66 [Google Scholar]
  135. Xiong Y, Huang CH, Iglesias PA, Devreotes PN. 2010. Cells navigate with a local-excitation, global-inhibition-biased excitable network. PNAS 107:17079–86 [Google Scholar]
  136. Yang HW, Collins SR, Meyer T. 2016. Locally excitable Cdc42 signals steer cells during chemotaxis. Nat. Cell Biol. 18:191–201 [Google Scholar]
  137. Yang X, Dormann D, Münsterberg AE, Weijer CJ. 2002. Cell movement patterns during gastrulation in the chick are controlled by positive and negative chemotaxis mediated by FGF4 and FGF8. Dev. Cell 3:425–37 [Google Scholar]
  138. Yoshida K, Soldati T. 2006. Dissection of amoeboid movement into two mechanically distinct modes. J. Cell Sci. 119:3833–44 [Google Scholar]
  139. Zhang S, Charest PG, Firtel RA. 2008. Spatiotemporal regulation of Ras activity provides directional sensing. Curr. Biol. 18:1587–93 [Google Scholar]
  140. Zhao M, Jin T, McCaig CD, Forrester JV, Devreotes PN. 2002. Genetic analysis of the role of G protein–coupled receptor signaling in electrotaxis. J. Cell Biol. 157:921–27 [Google Scholar]
  141. Zhao M, Song B, Pu J, Wada T, Reid B. et al. 2006. Electrical signals control wound healing through phosphatidylinositol-3-OH kinase-γ and PTEN. Nature 442:457–60 [Google Scholar]

Data & Media loading...

Supplementary Data

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error