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Cell Migration: An Overview

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Cell Migration

Part of the book series: Methods in Molecular Biology ((MIMB,volume 769))

Abstract

Cell migration is a fundamental process that controls morphogenesis and inflammation. Its deregulation causes or is part of many diseases, including autoimmune syndromes, chronic inflammation, mental retardation, and cancer. Cell migration is an integral part of the cell biology, embryology, immunology, and neuroscience fields; as such, it has benefited from quantum leaps in molecular biology, biochemistry, and imaging techniques, and the emergence of the genomic and proteomic era. Combinations of these techniques have revealed new and exciting insights that explain how cells adhere and move, how the migration of multiple cells are coordinated and regulated, and how the cells interact with neighboring cells and/or react to changes in their microenvironment. This introduction provides a primer of the molecular and cellular insights, particularly the signaling networks, which control the migration of individual cells as well as collective migrations. The rest of the chapters are devoted to describe in detail some of the most salient technical advances that have illuminated the field of cell migration in recent years.

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References

  1. Ridley AJ, Schwartz MA, Burridge K et al. Cell migration: integrating signals from front to back. Science, 302(5651), 1704–1709 (2003).

    PubMed  CAS  Google Scholar 

  2. Friedl P, Wolf K. Plasticity of cell migration: a multiscale tuning model. J Cell Biol, 188(1), 11–19 (2010).

    PubMed  CAS  Google Scholar 

  3. Olson MF, Sahai E. The actin cytoskeleton in cancer cell motility. Clin Exp Metastasis, 26(4), 273–287 (2009).

    PubMed  Google Scholar 

  4. Stephens L, Milne L, Hawkins P. Moving towards a better understanding of chemotaxis. Curr Biol, 18(11), R485–494 (2008).

    PubMed  CAS  Google Scholar 

  5. Gaggioli C, Hooper S, Hidalgo-Carcedo C et al. Fibroblast-led collective invasion of carcinoma cells with differing roles for RhoGTPases in leading and following cells. Nat Cell Biol, 9(12), 1392–1400 (2007).

    PubMed  CAS  Google Scholar 

  6. Hatten ME. New directions in neuronal migration. Science, 297(5587), 1660–1663 (2002).

    PubMed  CAS  Google Scholar 

  7. Weijer CJ. Collective cell migration in development. J Cell Sci, 122(Pt 18), 3215–3223 (2009).

    PubMed  CAS  Google Scholar 

  8. Korn ED, Carlier MF, Pantaloni D. Actin polymerization and ATP hydrolysis. Science, 238(4827), 638–644 (1987).

    PubMed  CAS  Google Scholar 

  9. Pollard TD, Borisy GG. Cellular motility driven by assembly and disassembly of actin filaments. Cell, 112(4), 453–465 (2003).

    PubMed  CAS  Google Scholar 

  10. Pollard TD, Cooper JA. Actin, a central player in cell shape and movement. Science, 326(5957), 1208–1212 (2009).

    PubMed  CAS  Google Scholar 

  11. Block J, Stradal TE, Hanisch J et al. Filopodia formation induced by active mDia2/Drf3. J Microsc, 231(3), 506–517 (2008).

    PubMed  CAS  Google Scholar 

  12. Mattila PK, Lappalainen P. Filopodia: molecular architecture and cellular functions. Nat Rev Mol Cell Biol, 9(6), 446–454 (2008).

    PubMed  CAS  Google Scholar 

  13. Mejillano MR, Kojima S, Applewhite DA et al. Lamellipodial versus filopodial mode of the actin nanomachinery: pivotal role of the filament barbed end. Cell, 118(3), 363–373 (2004).

    PubMed  CAS  Google Scholar 

  14. Cramer LP, Siebert M, Mitchison TJ. Identification of novel graded polarity actin filament bundles in locomoting heart fibroblasts: implications for the generation of motile force. J Cell Biol, 136(6), 1287–1305 (1997).

    PubMed  CAS  Google Scholar 

  15. Svitkina TM, Borisy GG. Arp2/3 complex and actin depolymerizing factor/cofilin in dendritic organization and treadmilling of actin filament array in lamellipodia. J Cell Biol, 145(5), 1009–1026 (1999).

    PubMed  CAS  Google Scholar 

  16. Ponti A, Machacek M, Gupton SL, Waterman-Storer CM, Danuser G. Two distinct actin networks drive the protrusion of migrating cells. Science, 305(5691), 1782–1786 (2004).

    PubMed  CAS  Google Scholar 

  17. Koestler SA, Auinger S, Vinzenz M, Rottner K, Small JV. Differentially oriented populations of actin filaments generated in lamellipodia collaborate in pushing and pausing at the cell front. Nat Cell Biol, 10(3), 306–313 (2008).

    PubMed  CAS  Google Scholar 

  18. Vallotton P, Small JV. Shifting views on the leading role of the lamellipodium in cell migration: speckle tracking revisited. J Cell Sci, 122(Pt 12), 1955–1958 (2009).

    PubMed  CAS  Google Scholar 

  19. Danuser G. Testing the lamella hypothesis: the next steps on the agenda. J Cell Sci, 122(Pt 12), 1959–1962 (2009).

    PubMed  CAS  Google Scholar 

  20. Chrzanowska-Wodnicka M, Burridge K. Rho-stimulated contractility drives the formation of stress fibers and focal adhesions. J Cell Biol, 133(6), 1403–1415 (1996).

    PubMed  CAS  Google Scholar 

  21. Hotulainen P, Lappalainen P. Stress fibers are generated by two distinct actin assembly mechanisms in motile cells. J Cell Biol, 173(3), 383–394 (2006).

    PubMed  CAS  Google Scholar 

  22. Yarmola EG, Bubb MR. Profilin: emerging concepts and lingering misconceptions. Trends Biochem Sci, 31(4), 197–205 (2006).

    PubMed  CAS  Google Scholar 

  23. Le Clainche C, Carlier M-F. Regulation of actin assembly associated with pprotrusion and adhesion in cell migration. Physiol. Rev., 88(2), 489–513 (2008).

    PubMed  Google Scholar 

  24. Kislauskis EH, Zhu X, Singer RH. beta-Actin messenger RNA localization and protein synthesis augment cell motility. J Cell Biol, 136(6), 1263–1270 (1997).

    PubMed  CAS  Google Scholar 

  25. Condeelis J. How is actin polymerization nucleated in vivo? Trends Cell Biol, 11(7), 288–293 (2001).

    PubMed  CAS  Google Scholar 

  26. Bamburg JR, Bernstein BW. ADF/cofilin. Curr Biol, 18(7), R273–275 (2008).

    PubMed  CAS  Google Scholar 

  27. Maciver SK, Hussey PJ. The ADF/cofilin family: actin-remodeling proteins. Genome Biol, 3(5), reviews3007 (2002).

    Google Scholar 

  28. Uetrecht AC, Bear JE. Coronins: the return of the crown. Trends Cell Biol, 16(8), 421–426 (2006).

    PubMed  CAS  Google Scholar 

  29. Cai L, Marshall TW, Uetrecht AC, Schafer DA, Bear JE. Coronin 1B coordinates Arp2/3 complex and cofilin activities at the leading edge. Cell, 128(5), 915–929 (2007).

    PubMed  CAS  Google Scholar 

  30. Campellone KG, Welch MD. A nucleator arms race: cellular control of actin assembly. Nat Rev Mol Cell Biol, 11(4), 237–251 (2010).

    PubMed  CAS  Google Scholar 

  31. Paul AS, Pollard TD. Review of the mechanism of processive actin filament elongation by formins. Cell Motil Cytoskeleton, 66(8), 606–617 (2009).

    PubMed  CAS  Google Scholar 

  32. Chesarone MA, DuPage AG, Goode BL. Unleashing formins to remodel the actin and microtubule cytoskeletons. Nat Rev Mol Cell Biol, 11(1), 62–74 (2010).

    PubMed  CAS  Google Scholar 

  33. Bear JE, Gertler FB. Ena/VASP: towards resolving a pointed controversy at the barbed end. J Cell Sci, 122(Pt 12), 1947–1953 (2009).

    PubMed  CAS  Google Scholar 

  34. Bear JE, Svitkina TM, Krause M et al. Antagonism between Ena/VASP proteins and actin filament capping regulates fibroblast motility. Cell, 109(4), 509–521 (2002).

    PubMed  CAS  Google Scholar 

  35. Cooper JA, Schafer DA. Control of actin assembly and disassembly at filament ends. Curr Opin Cell Biol, 12(1), 97–103 (2000).

    PubMed  CAS  Google Scholar 

  36. Zigmond SH. Beginning and ending an actin filament: control at the barbed end. Curr Top Dev Biol, 63, 145–188 (2004).

    PubMed  CAS  Google Scholar 

  37. Mullins RD, Heuser JA, Pollard TD. The interaction of Arp2/3 complex with actin: nucleation, high affinity pointed end capping, and formation of branching networks of ­filaments. Proc Natl Acad Sci USA, 95(11), 6181–6186 (1998).

    PubMed  CAS  Google Scholar 

  38. Thrasher AJ, Burns SO. WASP: a key immunological multitasker. Nat Rev Immunol, 10(3), 182–192 (2010).

    PubMed  CAS  Google Scholar 

  39. Nolen BJ, Pollard TD. Structure and biochemical properties of fission yeast Arp2/3 complex lacking the Arp2 subunit. J Biol Chem, 283(39), 26490–26498 (2008).

    PubMed  CAS  Google Scholar 

  40. Pollitt AY, Insall RH. WASP and SCAR/WAVE proteins: the drivers of actin asse­mbly. J Cell Sci, 122(Pt 15), 2575–2578 (2009).

    PubMed  CAS  Google Scholar 

  41. Vartiainen MK, Machesky LM. The WASP-Arp2/3 pathway: genetic insights. Curr Opin Cell Biol, 16(2), 174–181 (2004).

    PubMed  CAS  Google Scholar 

  42. Yang C, Czech L, Gerboth S et al. Novel roles of formin mDia2 in lamellipodia and filopodia formation in motile cells. PLoS Biol, 5(11), e317 (2007).

    PubMed  Google Scholar 

  43. Insall RH, Machesky LM. Actin dynamics at the leading edge: from simple machinery to complex networks. Dev Cell, 17(3), 310–322 (2009).

    PubMed  CAS  Google Scholar 

  44. Vicente-Manzanares M, Ma X, Adelstein RS, Horwitz AR. Non-muscle myosin II takes centre stage in cell adhesion and migration. Nat Rev Mol Cell Biol, 10(11), 778–790 (2009).

    PubMed  CAS  Google Scholar 

  45. Charras G, Paluch E. Blebs lead the way: how to migrate without lamellipodia. Nat Rev Mol Cell Biol, 9(9), 730–736 (2008).

    PubMed  CAS  Google Scholar 

  46. Fackler OT, Grosse R. Cell motility through plasma membrane blebbing. J Cell Biol, 181(6), 879–884 (2008).

    PubMed  CAS  Google Scholar 

  47. Gonczy P. Mechanisms of asymmetric cell division: flies and worms pave the way. Nat Rev Mol Cell Biol, 9(5), 355–366 (2008).

    PubMed  Google Scholar 

  48. Slaughter BD, Smith SE, Li R. Symmetry breaking in the life cycle of the budding yeast. Cold Spring Harb Perspect Biol, 1(3), a003384 (2009).

    PubMed  Google Scholar 

  49. Mellman I, Nelson WJ. Coordinated protein sorting, targeting and distribution in polarized cells. Nat Rev Mol Cell Biol, 9(11), 833–845 (2008).

    PubMed  CAS  Google Scholar 

  50. Li R, Gundersen GG. Beyond polymer polarity: how the cytoskeleton builds a polarized cell. Nat Rev Mol Cell Biol, 9(11), 860–873 (2008).

    PubMed  CAS  Google Scholar 

  51. Iden S, Collard JG. Crosstalk between small GTPases and polarity proteins in cell polarization. Nat Rev Mol Cell Biol, 9(11), 846–859 (2008).

    PubMed  CAS  Google Scholar 

  52. Goldstein B, Macara IG. The PAR proteins: fundamental players in animal cell polarization. Dev Cell, 13(5), 609–622 (2007).

    PubMed  CAS  Google Scholar 

  53. Johnson MH. From mouse egg to mouse embryo: polarities, axes, and tissues. Annu Rev Cell Dev Biol, 25, 483–512 (2009).

    PubMed  CAS  Google Scholar 

  54. Iglesias PA, Devreotes PN. Navigating through models of chemotaxis. Curr Opin Cell Biol, 20(1), 35–40 (2008).

    PubMed  CAS  Google Scholar 

  55. Swaney KF, Huang CH, Devreotes PN. Eukaryotic Chemotaxis: A Network of Signaling Pathways Controls Motility, Directional Sensing, and Polarity. Annu Rev Biophys, (2010).

    Google Scholar 

  56. Verkhovsky AB, Svitkina TM, Borisy GG. Self-polarization and directional motility of cytoplasm. Curr Biol, 9(1), 11–20 (1999).

    PubMed  CAS  Google Scholar 

  57. Yam PT, Wilson CA, Ji L et al. Actin-myosin network reorganization breaks symmetry at the cell rear to spontaneously initiate polarized cell motility. J Cell Biol, 178(7), 1207–1221 (2007).

    PubMed  CAS  Google Scholar 

  58. Vicente-Manzanares M, Koach MA, Whitmore L, Lamers ML, Horwitz AF. Segregation and activation of myosin IIB creates a rear in migrating cells. J Cell Biol, 183(3), 543–554 (2008).

    PubMed  CAS  Google Scholar 

  59. Mseka T, Coughlin M, Cramer LP. Graded actin filament polarity is the organization of oriented actomyosin II filament bundles required for fibroblast polarization. Cell Motil Cytoskeleton, 66(9), 743–753 (2009).

    PubMed  CAS  Google Scholar 

  60. Cotton M, Claing A. G protein-coupled receptors stimulation and the control of cell migration. Cell Signal, 21(7), 1045–1053 (2009).

    PubMed  CAS  Google Scholar 

  61. Xiao Z, Zhang N, Murphy DB, Devreotes PN. Dynamic distribution of chemoattractant receptors in living cells during chemotaxis and persistent stimulation. J Cell Biol, 139(2), 365–374 (1997).

    PubMed  CAS  Google Scholar 

  62. Servant G, Weiner OD, Neptune ER, Sedat JW, Bourne HR. Dynamics of a chemoattractant receptor in living neutrophils during chemotaxis. Mol Biol Cell, 10(4), 1163–1178 (1999).

    PubMed  CAS  Google Scholar 

  63. Van Haastert PJ, Devreotes PN. Chemotaxis: signalling the way forward. Nat Rev Mol Cell Biol, 5(8), 626–634 (2004).

    PubMed  Google Scholar 

  64. Kolsch V, Charest PG, Firtel RA. The regulation of cell motility and chemotaxis by phospholipid signaling. J Cell Sci, 121(Pt 5), 551–559 (2008).

    PubMed  CAS  Google Scholar 

  65. Cain RJ, Ridley AJ. Phosphoinositide 3-kinases in cell migration. Biol Cell, 101(1), 13–29 (2009).

    PubMed  CAS  Google Scholar 

  66. Garcia-Mata R, Burridge K. Catching a GEF by its tail. Trends Cell Biol, 17(1), 36–43 (2007).

    PubMed  CAS  Google Scholar 

  67. Iijima M, Devreotes P. Tumor suppressor PTEN mediates sensing of chemoattractant gradients. Cell, 109(5), 599–610 (2002).

    PubMed  CAS  Google Scholar 

  68. Funamoto S, Meili R, Lee S, Parry L, Firtel RA. Spatial and temporal regulation of 3-phosphoinositides by PI 3-kinase and PTEN mediates chemotaxis. Cell, 109(5), 611–623 (2002).

    PubMed  CAS  Google Scholar 

  69. Etienne-Manneville S, Hall A. Cell polarity: Par6, aPKC and cytoskeletal crosstalk. Curr Opin Cell Biol, 15(1), 67–72 (2003).

    PubMed  CAS  Google Scholar 

  70. Hoeller O, Kay RR. Chemotaxis in the absence of PIP3 gradients. Curr Biol, 17(9), 813–817 (2007).

    PubMed  CAS  Google Scholar 

  71. Heasman SJ, Ridley AJ. Mammalian Rho GTPases: new insights into their functions from in vivo studies. Nat Rev Mol Cell Biol, 9(9), 690–701 (2008).

    PubMed  CAS  Google Scholar 

  72. Etienne-Manneville S. Cdc42--the centre of polarity. J Cell Sci, 117(Pt 8), 1291–1300 (2004).

    PubMed  CAS  Google Scholar 

  73. Gerard A, Mertens AE, van der Kammen RA, Collard JG. The Par polarity complex regulates Rap1- and chemokine-induced T cell polarization. J Cell Biol, 176(6), 863–875 (2007).

    PubMed  CAS  Google Scholar 

  74. Osmani N, Vitale N, Borg JP, Etienne-Manneville S. Scrib controls Cdc42 localization and activity to promote cell polarization during astrocyte migration. Curr Biol, 16(24), 2395–2405 (2006).

    PubMed  CAS  Google Scholar 

  75. Nobes CD, Hall A. Rho, Rac, and Cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia. Cell, 81(1), 53–62 (1995).

    PubMed  CAS  Google Scholar 

  76. Gomez-Mouton C, Lacalle RA, Mira E et al. Dynamic redistribution of raft domains as an organizing platform for signaling during cell chemotaxis. J Cell Biol, 164(5), 759–768 (2004).

    PubMed  CAS  Google Scholar 

  77. Sander EE, ten Klooster JP, van Delft S, van der Kammen RA, Collard JG. Rac downregulates Rho activity: reciprocal balance between both GTPases determines cellular morphology and migratory behavior. J Cell Biol, 147(5), 1009–1022 (1999).

    PubMed  CAS  Google Scholar 

  78. Vicente-Manzanares M, Choi CK, Horwitz AR. Integrins in cell migration--the actin connection. J Cell Sci, 122(Pt 2), 199–206 (2009).

    PubMed  CAS  Google Scholar 

  79. Keren K, Pincus Z, Allen GM et al. Mechanism of shape determination in motile cells. Nature, 453(7194), 475–480 (2008).

    PubMed  CAS  Google Scholar 

  80. Sanchez-Madrid F, Serrador JM. Bringing up the rear: defining the roles of the uropod. Nat Rev Mol Cell Biol, 10(5), 353–359 (2009).

    PubMed  CAS  Google Scholar 

  81. Omelchenko T, Vasiliev JM, Gelfand IM, Feder HH, Bonder EM. Mechanisms of polarization of the shape of fibroblasts and epitheliocytes: Separation of the roles of microtubules and Rho-dependent actin-myosin contractility. Proc Natl Acad Sci USA, 99(16), 10452–10457 (2002).

    PubMed  CAS  Google Scholar 

  82. Ratner S, Sherrod WS, Lichlyter D. Microtubule retraction into the uropod and its role in T cell polarization and motility. J Immunol, 159(3), 1063–1067 (1997).

    PubMed  CAS  Google Scholar 

  83. Lansbergen G, Akhmanova A. Microtubule plus end: a hub of cellular activities. Traffic, 7(5), 499–507 (2006).

    PubMed  CAS  Google Scholar 

  84. Gomes ER, Jani S, Gundersen GG. Nuclear movement regulated by Cdc42, MRCK, myosin, and actin flow establishes MTOC polarization in migrating cells. Cell, 121(3), 451–463 (2005).

    PubMed  CAS  Google Scholar 

  85. Etienne-Manneville S, Hall A. Cdc42 regulates GSK-3beta and adenomatous polyposis coli to control cell polarity. Nature, 421(6924), 753–756 (2003).

    PubMed  CAS  Google Scholar 

  86. Schmoranzer J, Fawcett JP, Segura M et al. Par3 and dynein associate to regulate local microtubule dynamics and centrosome orientation during migration. Curr Biol, 19(13), 1065–1074 (2009).

    PubMed  CAS  Google Scholar 

  87. Curtis AS. The Mechanism of Adhesion of Cells to Glass. A Study by Interference Reflection Microscopy. J Cell Biol, 20, 199–215 (1964).

    CAS  Google Scholar 

  88. Lazarides E, Burridge K. Alpha-actinin: immunofluorescent localization of a muscle structural protein in nonmuscle cells. Cell, 6(3), 289–298 (1975).

    PubMed  CAS  Google Scholar 

  89. Izzard CS, Lochner LR. Cell-to-substrate contacts in living fibroblasts: an interference reflexion study with an evaluation of the technique. J Cell Sci, 21(1), 129–159 (1976).

    PubMed  CAS  Google Scholar 

  90. Heath JP, Dunn GA. Cell to substratum contacts of chick fibroblasts and their relation to the microfilament system. A correlated interference-reflexion and high-voltage electron-microscope study. J Cell Sci, 29, 197–212 (1978).

    CAS  Google Scholar 

  91. Geiger B. A 130K protein from chicken gizzard: its localization at the termini of microfilament bundles in cultured chicken cells. Cell, 18(1), 193–205 (1979).

    PubMed  CAS  Google Scholar 

  92. Alexandrova AY, Arnold K, Schaub S et al. Comparative dynamics of retrograde actin flow and focal adhesions: formation of nascent adhesions triggers transition from fast to slow flow. PLoS One, 3(9), e3234 (2008).

    PubMed  Google Scholar 

  93. Choi CK, Vicente-Manzanares M, Zareno J et al. Actin and alpha-actinin orchestrate the assembly and maturation of nascent adhesions in a myosin II motor-independent manner. Nat Cell Biol, 10(9), 1039–1050 (2008).

    PubMed  CAS  Google Scholar 

  94. Zaidel-Bar R, Ballestrem C, Kam Z, Geiger B. Early molecular events in the assembly of matrix adhesions at the leading edge of migrating cells. J Cell Sci, 116(Pt 22), 4605–4613 (2003).

    PubMed  CAS  Google Scholar 

  95. Giannone G, Dubin-Thaler BJ, Rossier O et al. Lamellipodial actin mechanically links myosin activity with adhesion-site formation. Cell, 128(3), 561–575 (2007).

    PubMed  CAS  Google Scholar 

  96. Rottner K, Hall A, Small JV. Interplay between Rac and Rho in the control of substrate contact dynamics. Current Biology, 9(12), 640–649 (1999).

    PubMed  CAS  Google Scholar 

  97. Zaidel-Bar R, Cohen M, Addadi L, Geiger B. Hierarchical assembly of cell-matrix adhesion complexes. Biochem Soc Trans, 32(Pt 3), 416–420 (2004).

    Google Scholar 

  98. Calle Y, Anton IM, Thrasher AJ, Jones GE. WASP and WIP regulate podosomes in migrating leukocytes. J Microsc, 231(3), 494–505 (2008).

    PubMed  CAS  Google Scholar 

  99. Gimona M, Buccione R, Courtneidge SA, Linder S. Assembly and biological role of podosomes and invadopodia. Curr Opin Cell Biol, 20(2), 235–241 (2008).

    PubMed  CAS  Google Scholar 

  100. Buccione R, Orth JD, McNiven MA. Foot and mouth: podosomes, invadopodia and circular dorsal ruffles. Nat Rev Mol Cell Biol, 5(8), 647–657 (2004).

    PubMed  CAS  Google Scholar 

  101. Lener T, Burgstaller G, Crimaldi L, Lach S, Gimona M. Matrix-degrading podosomes in smooth muscle cells. Eur J Cell Biol, 85(3–4), 183–189 (2006).

    PubMed  CAS  Google Scholar 

  102. Block MR, Badowski C, Millon-Fremillon A et al. Podosome-type adhesions and focal adhesions, so alike yet so different. Eur J Cell Biol, 87(8–9), 491–506 (2008).

    PubMed  CAS  Google Scholar 

  103. Linder S. Invadosomes at a glance. J Cell Sci, 122(Pt 17), 3009–3013 (2009).

    PubMed  CAS  Google Scholar 

  104. Hynes RO. Integrins: bidirectional, allosteric signaling machines. Cell, 110(6), 673–687 (2002).

    PubMed  CAS  Google Scholar 

  105. Humphries JD, Byron A, Humphries MJ. Integrin ligands at a glance. J Cell Sci, 119(Pt 19), 3901–3903 (2006).

    PubMed  CAS  Google Scholar 

  106. Kim M, Carman CV, Springer TA. Bidirectional transmembrane signaling by cytoplasmic domain separation in integrins. Science, 301(5640), 1720–1725 (2003).

    PubMed  CAS  Google Scholar 

  107. Ye F, Hu G, Taylor D et al. Recreation of the terminal events in physiological integrin activation. J Cell Biol, 188(1), 157–173 (2010).

    PubMed  CAS  Google Scholar 

  108. Shattil SJ, Kim C, Ginsberg MH. The final steps of integrin activation: the end game. Nat Rev Mol Cell Biol, 11(4), 288–300 (2010).

    PubMed  CAS  Google Scholar 

  109. Askari JA, Tynan CJ, Webb SE et al. Focal adhesions are sites of integrin extension. J Cell Biol, 188(6), 891–903 (2010).

    PubMed  CAS  Google Scholar 

  110. Schwartz MA, Ginsberg MH. Networks and crosstalk: integrin signalling spreads. Nat Cell Biol, 4(4), E65–68 (2002).

    PubMed  CAS  Google Scholar 

  111. Carman CV, Springer TA. Integrin avidity regulation: are changes in affinity and conformation underemphasized? Curr Opin Cell Biol, 15(5), 547–556 (2003).

    PubMed  CAS  Google Scholar 

  112. Krauss K, Altevogt P. Integrin leukocyte function-associated antigen-1-mediated cell binding can be activated by clustering of membrane rafts. J Biol Chem, 274(52), 36921–36927 (1999).

    PubMed  CAS  Google Scholar 

  113. Hemler ME. Tetraspanin functions and associated microdomains. Nat Rev Mol Cell Biol, 6(10), 801–811 (2005).

    PubMed  CAS  Google Scholar 

  114. Yanez-Mo M, Barreiro O, Gordon-Alonso M, Sala-Valdes M, Sanchez-Madrid F. Tetraspanin-enriched microdomains: a functional unit in cell plasma membranes. Trends Cell Biol, 19(9), 434–446 (2009).

    PubMed  CAS  Google Scholar 

  115. Horwitz A, Duggan K, Buck C, Beckerle MC, Burridge K. Interaction of plasma membrane fibronectin receptor with talin--a transmembrane linkage. Nature, 320(6062), 531–533 (1986).

    PubMed  CAS  Google Scholar 

  116. Critchley DR. Biochemical and structural properties of the integrin-associated cytoskeletal protein talin. Annu Rev Biophys, 38, 235–254 (2009).

    PubMed  CAS  Google Scholar 

  117. Burridge K, Mangeat P. An interaction between vinculin and talin. Nature, 308(5961), 744–746 (1984).

    PubMed  CAS  Google Scholar 

  118. Hemmings L, Rees DJ, Ohanian V et al. Talin contains three actin-binding sites each of which is adjacent to a vinculin-binding site. J Cell Sci, 109 (Pt 11), 2715–2726 (1996).

    PubMed  CAS  Google Scholar 

  119. DeMali KA, Barlow CA, Burridge K. Recruitment of the Arp2/3 complex to vinculin: coupling membrane protrusion to matrix adhesion. J Cell Biol, 159(5), 881–891 (2002).

    PubMed  CAS  Google Scholar 

  120. Otey CA, Pavalko FM, Burridge K. An interaction between alpha-actinin and the beta 1 integrin subunit in vitro. J Cell Biol, 111(2), 721–729 (1990).

    PubMed  CAS  Google Scholar 

  121. Gilmore AP, Burridge K. Regulation of vinculin binding to talin and actin by phosphatidyl-inositol-4-5-bisphosphate. Nature, 381(6582), 531–535 (1996).

    PubMed  CAS  Google Scholar 

  122. Pfaff M, Liu S, Erle DJ, Ginsberg MH. Integrin beta cytoplasmic domains differentially bind to cytoskeletal proteins. J Biol Chem, 273(11), 6104–6109 (1998).

    PubMed  CAS  Google Scholar 

  123. Bakolitsa C, Cohen DM, Bankston LA et al. Structural basis for vinculin activation at sites of cell adhesion. Nature, 430(6999), 583–586 (2004).

    PubMed  CAS  Google Scholar 

  124. Izaguirre G, Aguirre L, Hu YP et al. The cytoskeletal/non-muscle isoform of alpha-actinin is phosphorylated on its actin-binding domain by the focal adhesion kinase. J Biol Chem, 276(31), 28676–28685 (2001).

    PubMed  CAS  Google Scholar 

  125. Jiang G, Giannone G, Critchley DR, Fukumoto E, Sheetz MP. Two-piconewton slip bond between fibronectin and the cytoskeleton depends on talin. Nature, 424(6946), 334–337 (2003).

    PubMed  CAS  Google Scholar 

  126. del Rio A, Perez-Jimenez R, Liu R et al. Stretching single talin rod molecules activates vinculin binding. Science, 323(5914), 638–641 (2009).

    PubMed  Google Scholar 

  127. Friedland JC, Lee MH, Boettiger D. Mechanically activated integrin switch controls alpha5beta1 function. Science, 323(5914), 642–644 (2009).

    PubMed  CAS  Google Scholar 

  128. Ballestrem C, Erez N, Kirchner J et al. Molecular mapping of tyrosine-phosphorylated proteins in focal adhesions using fluorescence resonance energy transfer. J Cell Sci, 119(Pt 5), 866–875 (2006).

    PubMed  CAS  Google Scholar 

  129. Parsons JT. Focal adhesion kinase: the first ten years. J Cell Sci, 116(Pt 8), 1409–1416 (2003).

    PubMed  CAS  Google Scholar 

  130. Webb DJ, Donais K, Whitmore LA et al. FAK-Src signalling through paxillin, ERK and MLCK regulates adhesion disassembly. Nat Cell Biol, 6(2), 154–161 (2004).

    PubMed  CAS  Google Scholar 

  131. Tomar A, Schlaepfer DD. Focal adhesion kinase: switching between GAPs and GEFs in the regulation of cell motility. Curr Opin Cell Biol, 21(5), 676–683 (2009).

    PubMed  CAS  Google Scholar 

  132. Deakin NO, Turner CE. Paxillin comes of age. J Cell Sci, 121(Pt 15), 2435–2444 (2008).

    PubMed  CAS  Google Scholar 

  133. Defilippi P, Di Stefano P, Cabodi S. p130Cas: a versatile scaffold in signaling networks. Trends Cell Biol, 16(5), 257–263 (2006).

    PubMed  CAS  Google Scholar 

  134. Matsuda M, Ota S, Tanimura R et al. Interaction between the amino-terminal SH3 domain of CRK and its natural target proteins. J Biol Chem, 271(24), 14468–14472 (1996).

    PubMed  CAS  Google Scholar 

  135. Sawada Y, Tamada M, Dubin-Thaler BJ et al. Force sensing by mechanical extension of the Src family kinase substrate p130Cas. Cell, 127(5), 1015–1026 (2006).

    PubMed  CAS  Google Scholar 

  136. Drees BE, Andrews KM, Beckerle MC. Molecular dissection of zyxin function reveals its involvement in cell motility. J Cell Biol, 147(7), 1549–1560 (1999).

    PubMed  CAS  Google Scholar 

  137. Yoshigi M, Hoffman LM, Jensen CC, Yost HJ, Beckerle MC. Mechanical force mobilizes zyxin from focal adhesions to actin filaments and regulates cytoskeletal reinforcement. J Cell Biol, 171(2), 209–215 (2005).

    PubMed  CAS  Google Scholar 

  138. Hall EH, Daugherty AE, Choi CK, Horwitz AF, Brautigan DL. Tensin1 requires protein phosphatase-1alpha in addition to RhoGAP DLC-1 to control cell polarization, migration, and invasion. J Biol Chem, 284(50), 34713–34722 (2009).

    PubMed  CAS  Google Scholar 

  139. Zaidel-Bar R, Itzkovitz S, Ma’ayan A, Iyengar R, Geiger B. Functional atlas of the integrin adhesome. Nat Cell Biol, 9(8), 858–867 (2007).

    PubMed  CAS  Google Scholar 

  140. Zaidel-Bar R, Geiger B. The switchable integrin adhesome. J Cell Sci, 123(Pt 9), 1385–1388 (2010).

    PubMed  CAS  Google Scholar 

  141. Crowley E, Horwitz AF. Tyrosine phosphorylation and cytoskeletal tension regulate the release of fibroblast adhesions. J Cell Biol, 131(2), 525–537 (1995).

    PubMed  CAS  Google Scholar 

  142. Vicente-Manzanares M, Zareno J, Whitmore L, Choi CK, Horwitz AF. Regulation of protrusion, adhesion dynamics, and polarity by myosins IIA and IIB in migrating cells. J Cell Biol, 176(5), 573–580 (2007).

    PubMed  CAS  Google Scholar 

  143. Even-Ram S, Doyle AD, Conti MA et al. Myosin IIA regulates cell motility and actomyosin-microtubule crosstalk. Nat Cell Biol, 9(3), 299–309 (2007).

    PubMed  CAS  Google Scholar 

  144. Worthylake RA, Lemoine S, Watson JM, Burridge K. RhoA is required for monocyte tail retraction during transendothelial migration. J Cell Biol, 154(1), 147–160 (2001).

    PubMed  CAS  Google Scholar 

  145. Vicente-Manzanares M, Cabrero JR, Rey M et al. A role for the Rho-p160 Rho coiled-coil kinase axis in the chemokine stromal cell-derived factor-1alpha-induced lymphocyte actomyosin and microtubular organization and chemotaxis. J Immunol, 168(1), 400–410 (2002).

    PubMed  CAS  Google Scholar 

  146. Smith A, Bracke M, Leitinger B, Porter JC, Hogg N. LFA-1-induced T cell migration on ICAM-1 involves regulation of MLCK-mediated attachment and ROCK-dependent detachment. J Cell Sci, 116(Pt 15), 3123–3133 (2003).

    PubMed  CAS  Google Scholar 

  147. Eddy RJ, Pierini LM, Matsumura F, Maxfield FR. Ca2+-dependent myosin II activation is required for uropod retraction during neutrophil migration. J Cell Sci, 113 (Pt 7), 1287–1298 (2000).

    PubMed  CAS  Google Scholar 

  148. Kaverina I, Krylyshkina O, Small JV. Microtubule targeting of substrate contacts promotes their relaxation and dissociation. J Cell Biol, 146(5), 1033–1044 (1999).

    PubMed  CAS  Google Scholar 

  149. Ezratty EJ, Partridge MA, Gundersen GG. Microtubule-induced focal adhesion disassembly is mediated by dynamin and focal adhesion kinase. Nat Cell Biol, 7(6), 581–590 (2005).

    PubMed  CAS  Google Scholar 

  150. Caswell PT, Vadrevu S, Norman JC. Integrins: masters and slaves of endocytic transport. Nat Rev Mol Cell Biol, 10(12), 843–853 (2009).

    PubMed  CAS  Google Scholar 

  151. Pierini LM, Lawson MA, Eddy RJ, Hendey B, Maxfield FR. Oriented endocytic recycling of alpha5beta1 in motile neutrophils. Blood, 95(8), 2471–2480 (2000).

    PubMed  CAS  Google Scholar 

  152. Ezratty EJ, Bertaux C, Marcantonio EE, Gundersen GG. Clathrin mediates integrin endocytosis for focal adhesion disassembly in migrating cells. J Cell Biol, 187(5), 733–747 (2009).

    PubMed  CAS  Google Scholar 

  153. Huttenlocher A, Palecek SP, Lu Q et al. Regulation of cell migration by the calcium-dependent protease calpain. J Biol Chem, 272(52), 32719–32722 (1997).

    PubMed  CAS  Google Scholar 

  154. Chan KT, Bennin DA, Huttenlocher A. Regulation of adhesion dynamics by calpain-mediated proteolysis of focal adhesion kinase (FAK). J Biol Chem, 285(15), 11418–11426 (2010).

    PubMed  CAS  Google Scholar 

  155. Franco SJ, Rodgers MA, Perrin BJ et al. Calpain-mediated proteolysis of talin regulates adhesion dynamics. Nat Cell Biol, 6(10), 977–983 (2004).

    PubMed  CAS  Google Scholar 

  156. Willard SS, Devreotes PN. Signaling pathways mediating chemotaxis in the social amoeba, Dictyostelium discoideum. Eur J Cell Biol, 85(9–10), 897–904 (2006).

    CAS  Google Scholar 

  157. Shaulsky G, Kessin RH. The cold war of the social amoebae. Curr Biol, 17(16), R684–692 (2007).

    PubMed  CAS  Google Scholar 

  158. Katagiri K, Maeda A, Shimonaka M, Kinashi T. RAPL, a Rap1-binding molecule that mediates Rap1-induced adhesion through spatial regulation of LFA-1. Nat Immunol, 4(8), 741–748 (2003).

    PubMed  CAS  Google Scholar 

  159. Rossman KL, Der CJ, Sondek J. GEF means go: turning on RHO GTPases with guanine nucleotide-exchange factors. Nat Rev Mol Cell Biol, 6(2), 167–180 (2005).

    PubMed  CAS  Google Scholar 

  160. Ridley AJ, Hall A. The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors. Cell, 70(3), 389–399 (1992).

    PubMed  CAS  Google Scholar 

  161. Amano M, Ito M, Kimura K et al. Phosphorylation and activation of myosin by Rho-associated kinase (Rho-kinase). J Biol Chem, 271(34), 20246–20249 (1996).

    PubMed  CAS  Google Scholar 

  162. Kimura K, Ito M, Amano M et al. Regulation of myosin phosphatase by Rho and Rho-associated kinase (Rho-kinase). Science, 273(5272), 245–248 (1996).

    PubMed  CAS  Google Scholar 

  163. Watanabe N, Madaule P, Reid T et al. p140mDia, a mammalian homolog of Drosophila diaphanous, is a target protein for Rho small GTPase and is a ligand for profilin. Embo J, 16(11), 3044–3056 (1997).

    PubMed  CAS  Google Scholar 

  164. Watanabe N, Kato T, Fujita A, Ishizaki T, Narumiya S. Cooperation between mDia1 and ROCK in Rho-induced actin reorganization. Nat Cell Biol, 1(3), 136–143 (1999).

    PubMed  CAS  Google Scholar 

  165. Wen Y, Eng CH, Schmoranzer J et al. EB1 and APC bind to mDia to stabilize microtubules downstream of Rho and promote cell migration. Nat Cell Biol, 6(9), 820–830 (2004).

    PubMed  CAS  Google Scholar 

  166. Yamashiro S, Totsukawa G, Yamakita Y et al. Citron kinase, a Rho-dependent kinase, induces di-phosphorylation of regulatory light chain of myosin II. Mol Biol Cell, 14(5), 1745–1756 (2003).

    PubMed  CAS  Google Scholar 

  167. Ridley AJ, Paterson HF, Johnston CL, Diekmann D, Hall A. The small GTP-binding protein rac regulates growth factor-induced membrane ruffling. Cell, 70(3), 401–410 (1992).

    PubMed  CAS  Google Scholar 

  168. Bokoch GM. Biology of the p21-activated kinases. Annu Rev Biochem, 72, 743–781 (2003).

    PubMed  CAS  Google Scholar 

  169. Sanders LC, Matsumura F, Bokoch GM, de Lanerolle P. Inhibition of myosin light chain kinase by p21-activated kinase. Science, 283(5410), 2083–2085 (1999).

    PubMed  CAS  Google Scholar 

  170. Chew TL, Masaracchia RA, Goeckeler ZM, Wysolmerski RB. Phosphorylation of non-muscle myosin II regulatory light chain by p21-activated kinase (gamma-PAK). J Muscle Res Cell Motil, 19(8), 839–854 (1998).

    PubMed  CAS  Google Scholar 

  171. Yang N, Higuchi O, Ohashi K et al. Cofilin phosphorylation by LIM-kinase 1 and its role in Rac-mediated actin reorganization. Nature, 393(6687), 809–812 (1998).

    PubMed  CAS  Google Scholar 

  172. Wittmann T, Bokoch GM, Waterman-Storer CM. Regulation of microtubule destabilizing activity of Op18/stathmin downstream of Rac1. J Biol Chem, 279(7), 6196–6203 (2004).

    PubMed  CAS  Google Scholar 

  173. Machesky LM, Hall A. Role of actin polymerization and adhesion to extracellular matrix in Rac- and Rho-induced cytoskeletal reorganization. J Cell Biol, 138(4), 913–926 (1997).

    PubMed  CAS  Google Scholar 

  174. Machesky LM, Mullins RD, Higgs HN et al. Scar, a WASp-related protein, activates nucleation of actin filaments by the Arp2/3 complex. Proc Natl Acad Sci USA, 96(7), 3739–3744 (1999).

    PubMed  CAS  Google Scholar 

  175. Manser E, Leung T, Salihuddin H, Zhao ZS, Lim L. A brain serine/threonine protein kinase activated by Cdc42 and Rac1. Nature, 367(6458), 40–46 (1994).

    PubMed  CAS  Google Scholar 

  176. Symons M, Derry JM, Karlak B et al. Wiskott-Aldrich syndrome protein, a novel effector for the GTPase CDC42Hs, is implicated in actin polymerization. Cell, 84(5), 723–734 (1996).

    PubMed  CAS  Google Scholar 

  177. Machesky LM, Insall RH. Scar1 and the related Wiskott-Aldrich syndrome protein, WASP, regulate the actin cytoskeleton through the Arp2/3 complex. Curr Biol, 8(25), 1347–1356 (1998).

    PubMed  CAS  Google Scholar 

  178. Osman MA, Cerione RA. Iqg1p, a yeast homologue of the mammalian IQGAPs, mediates cdc42p effects on the actin cytoskeleton. J Cell Biol, 142(2), 443–455 (1998).

    PubMed  CAS  Google Scholar 

  179. Leung T, Chen XQ, Tan I, Manser E, Lim L. Myotonic dystrophy kinase-related Cdc42-binding kinase acts as a Cdc42 effector in promoting cytoskeletal reorganization. Mol Cell Biol, 18(1), 130–140 (1998).

    PubMed  CAS  Google Scholar 

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Acknowledgments

The authors regret the rather large number of studies that were not cited due to space constraints. Rick Horwitz’s work is supported by NIH grants GM23244 and the Cell Migration Consortium (U54 GM064346).

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Authors and Affiliations

  1. Department of Cell Biology, University of Virginia School of Medicine, Charlottesville, VA, USA

    Alan Rick Horwitz

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  1. Miguel Vicente-Manzanares
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Correspondence to Alan Rick Horwitz .

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Editors and Affiliations

  1. , Division of Cancer Studies, King's College London, London, SE1 1UL, United Kingdom

    Claire M. Wells

  2. Randall Division of Cell and, Molecular Biophysics, King's College London, London, SE1 1UL, United Kingdom

    Maddy Parsons

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Vicente-Manzanares, M., Horwitz, A.R. (2011). Cell Migration: An Overview. In: Wells, C., Parsons, M. (eds) Cell Migration. Methods in Molecular Biology, vol 769. Humana Press. https://doi.org/10.1007/978-1-61779-207-6_1

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  • DOI: https://doi.org/10.1007/978-1-61779-207-6_1

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