Abstract
Cell migration is necessary for several developmental processes in multicellular organisms. Furthermore, many physiological processes such as wound healing and immunological events in adult animals are dependent on cell migration. Consequently, defects in cell migration are linked to various diseases including immunological disorders as well as cancer progression and metastasis formation. Cell migration is driven by specific protrusive and contractile actin filament structures, but the types and relative contributions of these actin filament arrays vary depending on the cell type and the environment of the cell. In this chapter, we introduce the most important actin filament structures that contribute to mesenchymal and amoeboid cell migration modes and discuss the mechanisms by which the assembly and turnover of these structures are controlled by various actin-binding proteins.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Abercrombie M, Heaysman JEM, Pegrum SM (1970a) The locomotion of fibroblasts in culture I. Movements of the leading edge. Exp Cell Res 59:393–398. doi:10.1016/0014-4827(70)90646-4
Abercrombie M, Heaysman JEM, Pegrum SM (1970b) The locomotion of fibroblasts in culture. II. “Ruffling.”. Exp Cell Res 60:437–444. doi:10.1016/0014-4827(70)90537-9
Abraham VC, Krishnamurthi V, Taylor DL, Lanni F (1999) The actin-based nanomachine at the leading edge of migrating cells. Biophys J 77:1721–1732. doi:10.1016/S0006-3495(99)77018-9
Al-Alwan MM, Rowden G, Lee TD, West KA (2001) Fascin is involved in the antigen presentation activity of mature dendritic cells. J Immunol 166:338–345. doi:10.4049/jimmunol.166.1.338
Anderson TW, Vaughan AN, Cramer LP (2008) Retrograde flow and myosin II activity within the leading cell edge deliver F-actin to the lamella to seed the formation of graded polarity actomyosin II filament bundles in migrating fibroblasts. Mol Biol Cell 19:5006–5018. doi:10.1091/mbc.E08-01-0034
Andrianantoandro E, Pollard TD (2006) Mechanism of actin filament turnover by severing and nucleation at different concentrations of ADF/cofilin. Mol Cell 24:13–23. doi:10.1016/j.molcel.2006.08.006
Beach JR, Shao L, Remmert K et al (2014) Nonmuscle myosin II isoforms coassemble in living cells. Curr Biol 24:1160–1166. doi:10.1016/j.cub.2014.03.071
Bear JE, Rawls JF, Saxe CL (1998) SCAR, a WASP-related protein, isolated as a suppressor of receptor defects in late Dictyostelium development. J Cell Biol 142:1325–1335. doi:10.1083/jcb.142.5.1325
Bear JE, Svitkina TM, Krause M et al (2002) Antagonism between Ena/VASP proteins and actin filament capping regulates fibroblast motility. Cell 109:509–521. doi:10.1016/S0092-8674(02)00731-6
Bentley D, Toroian-Raymond A (1986) Disoriented pathfinding by pioneer neurone growth cones deprived of filopodia by cytochalasin treatment. Nature 323:712–715. doi:10.1038/323712a0
Bergert M, Chandradoss SD, Desai RA, Paluch E (2012) Cell mechanics control rapid transitions between blebs and lamellipodia during migration. Proc Natl Acad Sci U S A 109:14434–14439. doi:10.1073/pnas.1207968109
Bertling E, Hotulainen P, Mattila PK et al (2004) Cyclase-associated protein 1 (CAP1) promotes cofilin-induced actin dynamics in mammalian nonmuscle cells. Mol Biol Cell 15:2324–2334. doi:10.1091/mbc.E04-01-0048
Bertling E, Quintero-Monzon O, Mattila PK et al (2007) Mechanism and biological role of profilin-Srv2/CAP interaction. J Cell Sci 120:1225–1234. doi:10.1242/jcs.000158
Bhuwania R, Cornfine S, Fang Z et al (2012) Supervillin couples myosin-dependent contractility to podosomes and enables their turnover. J Cell Sci 125:2300–2314. doi:10.1242/jcs.100032
Blanchoin L, Amann KJ, Higgs HN et al (2000) Direct observation of dendritic actin filament networks nucleated by Arp2/3 complex and WASP/Scar proteins. Nature 404:1007–1011. doi:10.1038/35010008
Block J, Breitsprecher D, Kühn S et al (2012) FMNL2 drives actin-based protrusion and migration downstream of Cdc42. Curr Biol 22:1005–1012. doi:10.1016/j.cub.2012.03.064
Bornschlögl T (2013) How filopodia pull: what we know about the mechanics and dynamics of filopodia. Cytoskeleton (Hoboken) 70:590–603. doi:10.1002/cm.21130
Bovellan M, Romeo Y, Biro M et al (2014) Cellular control of cortical actin nucleation. Curr Biol 24:1628–1635. doi:10.1016/j.cub.2014.05.069
Bray D, White J (1988) Cortical flow in animal cells. Science 239:883–888. doi:10.1126/science.3277283
Breitsprecher D, Kiesewetter AK, Linkner J et al (2011a) Molecular mechanism of Ena/VASP-mediated actin-filament elongation. EMBO J 30:456–467. doi:10.1038/emboj.2010.348
Breitsprecher D, Koestler SA, Chizhov I et al (2011b) Cofilin cooperates with fascin to disassemble filopodial actin filaments. J Cell Sci 124:3305–3318. doi:10.1242/jcs.086934
Brieher WM, Coughlin M, Mitchison TJ (2004) Fascin-mediated propulsion of Listeria monocytogenes independent of frequent nucleation by the Arp2/3 complex. J Cell Biol 165:233–242. doi:10.1083/jcb.200311040
Broschat KO, Weber A, Burgess DR (1989) Tropomyosin stabilizes the pointed end of actin filaments by slowing depolymerization. Biochemistry 28:8501–8506. doi:10.1021/bi00447a035
Burnette DT, Manley S, Sengupta P et al (2011) A role for actin arcs in the leading-edge advance of migrating cells. Nat Cell Biol 13:371–381. doi:10.1038/ncb2205
Burnette DT, Shao L, Ott C et al (2014) A contractile and counterbalancing adhesion system controls the 3D shape of crawling cells. J Cell Biol 205:83–96. doi:10.1083/jcb.201311104
Campellone KG, Welch MD (2010) A nucleator arms race: cellular control of actin assembly. Nat Rev Mol Cell Biol 11:237–251. doi:10.1038/nrm2867
Carlier MF, Laurent V, Santolini J et al (1997) Actin depolymerizing factor (ADF/cofilin) enhances the rate of filament turnover: implication in actin-based motility. J Cell Biol 136:1307–1322. doi:10.1083/jcb.136.6.1307
Charras G, Paluch E (2008) Blebs lead the way: how to migrate without lamellipodia. Nat Rev Mol Cell Biol 9:730–736. doi:10.1038/nrm2453
Charras GT, Hu C-KC-K, Coughlin M, Mitchison TJ (2006) Reassembly of contractile actin cortex in cell blebs. J Cell Biol 175:477–490. doi:10.1083/jcb.200602085
Chaudhry F, Breitsprecher D et al (2013) Srv2/cyclase-associated protein forms hexameric shurikens that directly catalyze actin filament severing by cofilin. Mol Biol Cell 24:31–41. doi:10.1091/mbc.E12-08-0589
Costa KD, Hucker WJ, Yin FCP (2002) Buckling of actin stress fibers: A new wrinkle in the cytoskeletal tapestry. Cell Motil Cytoskeleton 52:266–274. doi:10.1002/cm.10056
Cox S, Rosten E, Monypenny J et al (2012) Bayesian localization microscopy reveals nanoscale podosome dynamics. Nat Methods 9:195–200. doi:10.1038/nmeth.1812
Cramer LP, Siebert M, Mitchison TJ (1997) Identification of novel graded polarity actin filament bundles in locomoting heart fibroblasts: Implications for the generation of motile force. J Cell Biol 136:1287–1305. doi:10.1083/jcb.136.6.1287
Cunningham CC (1995) Actin polymerization and intracellular solvent flow in cell surface blebbing. J Cell Biol 129:1589–1599. doi:0021-9525/95/06/1589/11
DeRosier DJ, Edds KT (1980) Evidence for fascin cross-links between the actin filaments in coelomocyte filopodia. Exp Cell Res 126:490–494. doi:10.1016/0014-4827(80)90295-5
Deryugina EI, Ratnikov B, Monosov E et al (2001) MT1-MMP initiates activation of pro-MMP-2 and integrin alphavbeta3 promotes maturation of MMP-2 in breast carcinoma cells. Exp Cell Res 263:209–223. doi:10.1006/excr.2000.5118
Destaing O, Saltel F, Géminard J-C et al (2003) Podosomes display actin turnover and dynamic self-organization in osteoclasts expressing actin-green fluorescent protein. Mol Biol Cell 14:407–416. doi:10.1091/mbc.E02-07-0389
Disanza A, Mantoani S, Hertzog M et al (2006) Regulation of cell shape by Cdc42 is mediated by the synergic actin-bundling activity of the Eps8-IRSp53 complex. Nat Cell Biol 8:1337–1347. doi:10.1038/ncb1502
Discher DE, Janmey P, Wang Y-L (2005) Tissue cells feel and respond to the stiffness of their substrate. Science 310:1139–1143. doi:10.1126/science.1116995
Doyle AD, Petrie RJ, Kutys ML, Yamada KM (2013) Dimensions in cell migration. Curr Opin Cell Biol 25:642–649. doi:10.1016/j.ceb.2013.06.004
Edlund M, Lotano MA, Otey CA (2001) Dynamics of alpha-actinin in focal adhesions and stress fibers visualized with alpha-actinin-green fluorescent protein. Cell Motil Cytoskeleton 48:190–200. doi:10.1002/1097-0169(200103)48:3<190::AID-CM1008>3.0.CO;2-C
Elkhatib N, Neu MB, Zensen C et al (2014) Fascin plays a role in stress fiber organization and focal adhesion disassembly. Curr Biol 24:1492–1499. doi:10.1016/j.cub.2014.05.023
Euteneuer U, Schliwa M (1984) Persistent, directional motility of cells and cytoplasmic fragments in the absence of microtubules. Nature 310:58–61. doi:10.1038/310058a0
Franke RP, Gräfe M, Schnittler H et al (1984) Induction of human vascular endothelial stress fibres by fluid shear stress. Nature 307:648–649. doi:10.1038/307648a0
Friedl P, Alexander S (2011) Cancer invasion and the microenvironment: plasticity and reciprocity. Cell 147:992–1009. doi:10.1016/j.cell.2011.11.016
Galbraith CG, Yamada KM, Galbraith JA (2007) Polymerizing actin fibers position integrins primed to probe for adhesion sites. Science 315:992–995. doi:10.1126/science.1137904
Gallo G, Letourneau PC (2004) Regulation of growth cone actin filaments by guidance cues. J Neurobiol 58:92–102. doi:10.1002/neu.10282
Gandhi M, Smith BA, Bovellan M et al (2010) GMF is a cofilin homolog that binds Arp2/3 complex to stimulate filament debranching and inhibit actin nucleation. Curr Biol 20:861–867. doi:10.1016/j.cub.2010.03.026
Gateva G, Tojkander S, Koho S et al (2014) Palladin promotes assembly of non-contractile dorsal stress fibers through VASP recruitment. J Cell Sci 127:1887–1898. doi:10.1242/jcs.135780
Geiger B, Yamada KM (2011) Molecular architecture and function of matrix adhesions. Cold Spring Harb Perspect Biol 3:a005033. doi:10.1101/cshperspect.a005033
Geiger B, Spatz JP, Bershadsky AD (2009) Environmental sensing through focal adhesions. Nat Rev Mol Cell Biol 10:21–33. doi:10.1038/nrm2593
Giannone G, Dubin-Thaler BJ, Rossier O et al (2007) Lamellipodial actin mechanically links myosin activity with adhesion-site formation. Cell 128:561–575. doi:10.1016/j.cell.2006.12.039
Golomb E, Ma X, Jana SS et al (2004) Identification and characterization of nonmuscle myosin II-C, a new member of the myosin II family. J Biol Chem 279:2800–2808. doi:10.1074/jbc.M309981200
Gressin L, Guillotin A, Guérin C et al (2015) Architecture dependence of actin filament network disassembly. Curr Biol 25:1437–1447. doi:10.1016/j.cub.2015.04.011
Gunning P, O’Neill G, Hardeman E (2008) Tropomyosin-based regulation of the actin cytoskeleton in time and space. Physiol Rev 88:1–35. doi:10.1152/physrev.00001.2007
Gunning PW, Hardeman EC, Lappalainen P, Mulvihill DP (2015) Tropomyosin - master regulator of actin filament function in the cytoskeleton. J Cell Sci 128:2965–2974. doi:10.1242/jcs.172502
Gupton SL, Anderson KL, Kole TP et al (2005) Cell migration without a lamellipodium: translation of actin dynamics into cell movement mediated by tropomyosin. J Cell Biol 168:619–631. doi:10.1083/jcb.200406063
Haeger A, Wolf K, Zegers MM, Friedl P (2015) Collective cell migration: guidance principles and hierarchies. Trends Cell Biol 25:556–566. doi:10.1016/j.tcb.2015.06.003
Hawkins RJ, Piel M, Faure-Andre G et al (2009) Pushing off the walls: a mechanism of cell motility in confinement. Phys Rev Lett 102:058103. doi:10.1103/PhysRevLett.102.058103
Haynes EM, Asokan SB, King SJ et al (2015) GMFβ controls branched actin content and lamellipodial retraction in fibroblasts. J Cell Biol 209:803–812. doi:10.1083/jcb.201501094
Heasman SJ, Ridley AJ (2008) Mammalian Rho GTPases: new insights into their functions from in vivo studies. Nat Rev Mol Cell Biol 9:690–701. doi:10.1038/nrm2476
Heath JP (1983) Behaviour and structure of the leading lamella in moving fibroblasts. I. Occurrence and centripetal movement of arc-shaped microfilament bundles beneath the dorsal cell surface. J Cell Sci 60:331–354. doi:10.1016/0309-1651(81)90079-5
Hinz B, Mastrangelo D, Iselin CE et al (2001) Mechanical tension controls granulation tissue contractile activity and myofibroblast differentiation. Am J Pathol 159:1009–1020. doi:10.1016/S0002-9440(10)61776-2
Hitchcock-DeGregori SE, Sampath P, Pollard TD (1988) Tropomyosin inhibits the rate of actin polymerization by stabilizing actin filaments. Biochemistry 27:9182–9185. doi:10.1021/bi00426a016
Hoshino D, Branch KM, Weaver AM (2013) Signaling inputs to invadopodia and podosomes. J Cell Sci 126:2979–2989. doi:10.1242/jcs.079475
Hotulainen P, Lappalainen P (2006) Stress fibers are generated by two distinct actin assembly mechanisms in motile cells. J Cell Biol 173:383–394. doi:10.1083/jcb.200511093
Hotulainen P, Paunola E, Vartiainen MK, Lappalainen P (2005) Actin-depolymerizing factor and cofilin-1 play overlapping roles in promoting rapid F-actin depolymerization in mammalian nonmuscle cells. Mol Biol Cell 16:649–664. doi:10.1091/mbc.E04-07-0555
Isenberg G, Aebi U, Pollard TD (1980) An actin-binding protein from Acanthamoeba regulates actin filament polymerization and interactions. Nature 288:455–459. doi:10.1038/288455a0
Iwasa JH, Mullins RD (2007) Spatial and temporal relationships between actin-filament nucleation, capping, and disassembly. Curr Biol 17:395–406. doi:10.1016/j.cub.2007.02.012
Jaiswal R, Breitsprecher D, Collins A et al (2013) The formin Daam1 and fascin directly collaborate to promote filopodia formation. Curr Biol 23:1373–1379. doi:10.1016/j.cub.2013.06.013
Jansen S, Collins A, Chin SM et al (2015) Single-molecule imaging of a three-component ordered actin disassembly mechanism. Nat Commun 6:7202. doi:10.1038/ncomms8202
Jiu Y, Lehtimäki J, Tojkander S et al (2015) Bidirectional interplay between vimentin intermediate filaments and contractile actin stress fibers. Cell Rep 11:1511–1518. doi:10.1016/j.celrep.2015.05.008
Johnston AB, Collins A, Goode BL (2015) High-speed depolymerization at actin filament ends jointly catalysed by Twinfilin and Srv2/CAP. Nat Cell Biol. doi:10.1038/ncb3252
Kardash E, Reichman-Fried M, Maître J-L et al (2010) A role for Rho GTPases and cell-cell adhesion in single-cell motility in vivo. Nat Cell Biol 12:47–53. doi:10.1038/ncb2003
Katsuragawa Y, Yanagisawa M, Inoue a, Masaki T (1989) Two distinct nonmuscle myosin-heavy-chain mRNAs are differentially expressed in various chicken tissues. Identification of a novel gene family of vertebrate non-sarcomeric myosin heavy chains. Eur J Biochem 184:611–616. doi:10.1111/j.1432-1033.1989.tb15057.x
Kaverina I, Stradal TEB, Gimona M (2003) Podosome formation in cultured A7r5 vascular smooth muscle cells requires Arp2/3-dependent de-novo actin polymerization at discrete microdomains. J Cell Sci 116:4915–4924. doi:10.1242/jcs.00818
Kawamoto S, Adelstein R (1991) Chicken nonmuscle myosin heavy chains: differential expression of two mRNAs and evidence for two different polypeptides. J Cell Biol 112:915–924. doi:0021-9525/91/03/915/10
Kiuchi T, Ohashi K, Kurita S, Mizuno K (2007) Cofilin promotes stimulus-induced lamellipodium formation by generating an abundant supply of actin monomers. J Cell Biol 177:465–476. doi:10.1083/jcb.200610005
Kolega J (2003) Asymmetric distribution of IIB in migrating endothelial cells is regulated by a Rho-dependent kinase and contributes to tail retraction. Mol Biol Cell 14:4745–4757. doi:10.1091/mbc.E03
Korobova F, Svitkina T (2008) Arp2/3 complex is important for filopodia formation, growth cone motility, and neuritogenesis in neuronal cells. Mol Biol Cell 19:1561–1574. doi:10.1091/mbc.E07-09-0964
Kovac B, Teo JL, Mäkelä TP, Vallenius T (2013) Assembly of non-contractile dorsal stress fibers requires α-actinin-1 and Rac1 in migrating and spreading cells. J Cell Sci 126:263–273. doi:10.1242/jcs.115063
Kovar DR, Kuhn JR, Tichy AL, Pollard TD (2003) The fission yeast cytokinesis formin Cdc12p is a barbed end actin filament capping protein gated by profilin. J Cell Biol 161:875–887. doi:10.1083/jcb.200211078
Kress H, Stelzer EHK, Holzer D et al (2007) Filopodia act as phagocytic tentacles and pull with discrete steps and a load-dependent velocity. Proc Natl Acad Sci U S A 104:11633–11638. doi:10.1073/pnas.0702449104
Krugmann S, Jordens I, Gevaert K et al (2001) Cdc42 induces filopodia by promoting the formation of an IRSp53:Mena complex. Curr Biol 11:1645–1655. doi:10.1016/S0960-9822(01)00506-1
Lai FPL, Szczodrak M, Block J et al (2008) Arp2/3 complex interactions and actin network turnover in lamellipodia. EMBO J 27:982–992. doi:10.1038/emboj.2008.34
Lämmermann T, Bader BL, Monkley SJ et al (2008) Rapid leukocyte migration by integrin-independent flowing and squeezing. Nature 453:51–55. doi:10.1038/nature06887
Lewis WH, Lewis MR (1924) Behavior of cells in tissue cultures. In: Cowdry EV (ed) General cytology. The University of Chicago Press, Chicago, pp 385–447
Li R, Li G, Deng L et al (2010) IL-6 augments the invasiveness of U87MG human glioblastoma multiforme cells via up-regulation of MMP-2 and fascin-1. Oncol Rep 23:1553–1559. doi:10.3892/or_00000795
Lim KB, Bu W, Goh WI et al (2008) The Cdc42 effector IRSp53 generates filopodia by coupling membrane protrusion with actin dynamics. J Biol Chem 283:20454–20472. doi:10.1074/jbc.M710185200
Lim FY, Koon YL, Chiam K-H (2013) A computational model of amoeboid cell migration. Comput Methods Biomech Biomed Engin 16:1085–1095. doi:10.1080/10255842.2012.757598
Linder S, Wiesner C (2015) Tools of the trade: podosomes as multipurpose organelles of monocytic cells. Cell Mol Life Sci 72:121–135. doi:10.1007/s00018-014-1731-z
Linder S, Wiesner C, Himmel M (2011) Degrading devices: invadosomes in proteolytic cell invasion. Annu Rev Cell Dev Biol 27:185–211. doi:10.1146/annurev-cellbio-092910-154216
Lizárraga F, Poincloux R, Romão M et al (2009) Diaphanous-related formins are required for invadopodia formation and invasion of breast tumor cells. Cancer Res 69:2792–2800. doi:10.1158/0008-5472.CAN-08-3709
Logue JS, Cartagena-Rivera AX, Baird MA et al (2015) Erk regulation of actin capping and bundling by Eps8 promotes cortex tension and leader bleb-based migration. Elife 4, e08314. doi:10.7554/eLife.08314
Loisel TP, Boujemaa R, Pantaloni D, Carlier MF (1999) Reconstitution of actin-based motility of Listeria and Shigella using pure proteins. Nature 401:613–616. doi:10.1038/44183
Machesky LM, Insall RH (1998) Scar1 and the related Wiskott-Aldrich syndrome protein, WASP, regulate the actin cytoskeleton through the Arp2/3 complex. Curr Biol 8:1347–56. doi:10.1016/S0960-9822(98)00015-3
Machesky LM, Atkinson SJ, Ampe C, Vandekercldaove J (1994) Purification of a cortical complex containing two unconventional actins from acanthamoeba by affinity chromatography on profilin-agarose. J Cell Biol 127:107–115. doi:10.1083/jcb.127.1.107
Machesky LM, Mullins RD, Higgs HN et al (1999) Scar, a WASp-related protein, activates nucleation of actin filaments by the Arp2/3 complex. Proc Natl Acad Sci U S A 96:3739–3744. doi:10.1073/pnas.96.7.3739
Majumdar R, Sixt M, Parent CA (2014) New paradigms in the establishment and maintenance of gradients during directed cell migration. Curr Opin Cell Biol 30:33–40. doi:10.1016/j.ceb.2014.05.010
Mallavarapu A, Mitchison T (1999) Regulated actin cytoskeleton assembly at filopodium tips controls their extension and retraction. J Cell Biol 146:1097–1106. doi:10.1083/jcb.146.5.1097
Mattila PK, Lappalainen P (2008) Filopodia: molecular architecture and cellular functions. Nat Rev Mol Cell Biol 9:446–454. doi:10.1038/nrm2406
Mattila PK, Quintero-Monzon O, Kugler J et al (2004) A high-affinity interaction with ADP-actin monomers underlies the mechanism and in vivo function of Srv2/cyclase-associated protein. Mol Biol Cell 15:5158–5171. doi:10.1091/mbc.E04-06-0444
Mattila PK, Pykäläinen A, Saarikangas J et al (2007) Missing-in-metastasis and IRSp53 deform PI(4,5)P2-rich membranes by an inverse BAR domain-like mechanism. J Cell Biol 176:953–964. doi:10.1083/jcb.200609176
Maupin P, Phillips C, Adelstein R, Pollard T (1994) Differential localization of myosin-II isozymes in human cultured cells and blood cells. J Cell Sci 107:3077–3090
Medalia O, Beck M, Ecke M et al (2007) Organization of actin networks in intact filopodia. Curr Biol 17:79–84. doi:10.1016/j.cub.2006.11.022
Mejillano MR, Kojima S, Applewhite DA et al (2004) Lamellipodial versus filopodial mode of the actin nanomachinery. Cell 118:363–373. doi:10.1016/j.cell.2004.07.019
Miller J, Fraser SE, McClay D (1995) Dynamics of thin filopodia during sea urchin gastrulation. Development 121:2501–2511
Mogilner A, Rubinstein B (2005) The physics of filopodial protrusion. Biophys J 89:782–795. doi:10.1529/biophysj.104.056515
Moulding DA, Record J, Malinova D, Thrasher AJ (2013) Actin cytoskeletal defects in immunodeficiency. Immunol Rev 256:282–299. doi:10.1111/imr.12114
Mueller SC, Chen WT (1991) Cellular invasion into matrix beads: localization of beta 1 integrins and fibronectin to the invadopodia. J Cell Sci 99:213–225
Muller WA (2015) The regulation of transendothelial migration: new knowledge and new questions. Cardiovasc Res 107:310–320. doi:10.1093/cvr/cvv145
Mullins RD, Heuser JA, Pollard TD (1998) 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 U S A 95:6181–6186. doi:0027-8424y98y956181-6
Nemethova M, Auinger S, Small JV (2008) Building the actin cytoskeleton: Filopodia contribute to the construction of contractile bundles in the lamella. J Cell Biol 180:1233–1244. doi:10.1083/jcb.200709134
Norris AD, Dyer JO, Lundquist EA (2009) The Arp2/3 complex, UNC-115/abLIM, and UNC-34/Enabled regulate axon guidance and growth cone filopodia formation in Caenorhabditis elegans. Neural Dev 4:38. doi:10.1186/1749-8104-4-38
Nourshargh S, Hordijk PL, Sixt M (2010) Breaching multiple barriers: leukocyte motility through venular walls and the interstitium. Nat Rev Mol Cell Biol 11:366–378. doi:10.1038/nrm2889
Osiak AE, Zenner G, Linder S (2005) Subconfluent endothelial cells form podosomes downstream of cytokine and RhoGTPase signaling. Exp Cell Res 307:342–353. doi:10.1016/j.yexcr.2005.03.035
Otto JJ, Kane RE, Bryan J (1979) Formation of filopodia in coelomocytes: Localization of Fascin, a 58,000 Dalton actin cross-linking protein. Cell 17:285–293. doi:10.1016/0092-8674(79)90154-5
Paluch EK, Raz E (2013) The role and regulation of blebs in cell migration. Curr Opin Cell Biol 25:582–590. doi:10.1016/j.ceb.2013.05.005
Paluch E, Piel M, Prost J et al (2005) Cortical actomyosin breakage triggers shape oscillations in cells and cell fragments. Biophys J 89:724–733. doi:10.1529/biophysj.105.060590
Pantaloni D, Carlier M-F (1993) How profilin promotes actin filament assembly in the presence of thymosin β4. Cell 75:1007–1014. doi:10.1016/0092-8674(93)90544-Z
Parry DA, Squire JM (1973) Structural role of tropomyosin in muscle regulation: analysis of the x-ray diffraction patterns from relaxed and contracting muscles. J Mol Biol 75:33–55. doi:10.1016/0022-2836(73)90527-5
Pellegrin S, Mellor H (2007) Actin stress fibres. J Cell Sci 120:3491–3499. doi:10.1242/jcs.018473
Peng J, Wallar BJ, Flanders A et al (2003) Disruption of the Diaphanous-related formin Drf1 gene encoding mDia1 reveals a role for Drf3 as an effector for Cdc42. Curr Biol 13:534–45. doi:10.1016/S0960-9822(03)00170-2
Peter BJ, Kent HM, Mills IG et al (2004) BAR domains as sensors of membrane curvature: the amphiphysin BAR structure. Science 303:495–499. doi:10.1126/science.1092586
Petrie RJ, Yamada KM (2012) At the leading edge of three-dimensional cell migration. J Cell Sci 125:5917–5926. doi:10.1242/jcs.093732
Pfaff M, Jurdic P (2001) Podosomes in osteoclast-like cells: structural analysis and cooperative roles of paxillin, proline-rich tyrosine kinase 2 (Pyk2) and integrin alphaVbeta3. J Cell Sci 114:2775–2786
Pinner S, Sahai E (2008) PDK1 regulates cancer cell motility by antagonising inhibition of ROCK1 by RhoE. Nat Cell Biol 10:127–137. doi:10.1038/ncb1675
Poincloux R, Collin O, Lizárraga F et al (2011) Contractility of the cell rear drives invasion of breast tumor cells in 3D Matrigel. Proc Natl Acad Sci U S A 108:1943–1948. doi:10.1073/pnas.1010396108
Pollard TD (1986) Rate constants for the reactions of ATP- and ADP-actin with the ends of actin filaments. J Cell Biol 103:2747–2754. doi:0021-9525/86/12/2747/8
Pollard TD, Borisy GG (2003) Cellular motility driven by assembly and disassembly of actin filaments. Cell 112:453–465. doi:10.1016/S0092-8674(03)00120-X
Pollard TD, Cooper JA (2009) Actin, a central player in cell shape and movement. Science 326:1208–1212. doi:10.1126/science.1175862
Poukkula M, Hakala M, Pentinmikko N et al (2014) GMF promotes leading-edge dynamics and collective cell migration in vivo. Curr Biol 24:2533–2540. doi:10.1016/j.cub.2014.08.066
Prévost C, Zhao H, Manzi J et al (2015) IRSp53 senses negative membrane curvature and phase separates along membrane tubules. Nat Commun 6:8529. doi:10.1038/ncomms9529
Pruyne D, Evangelista M, Yang C et al (2002) Role of formins in actin assembly: nucleation and barbed-end association. Science 297:612–615. doi:10.1126/science.1072309
Puius YA, Mahoney NM, Almo SC (1998) The modular structure of actin-regulatory proteins. Curr Opin Cell Biol 10:23–34. doi:10.1016/S0955-0674(98)80083-5
Quintero-Monzon O, Jonasson EM, Bertling E et al (2009) Reconstitution and dissection of the 600-kDa Srv2/CAP complex: roles for oligomerization and cofilin-actin binding in driving actin turnover. J Biol Chem 284:10923–10934. doi:10.1074/jbc.M808760200
Reinhard M, Halbrügge M, Scheer U et al (1992) The 46/50 kDa phosphoprotein VASP purified from human platelets is a novel protein associated with actin filaments and focal contacts. EMBO J 11:2063–2070
Ridley AJ (2011) Life at the leading edge. Cell 145:1012–1022. doi:10.1016/j.cell.2011.06.010
Ridley AJ (2015) Rho GTPase signalling in cell migration. Curr Opin Cell Biol 36:103–112. doi:10.1016/j.ceb.2015.08.005
Ridley AJ, Hall A (1992) The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors. Cell 70:389–399. doi:10.1016/0092-8674(92)90163-7
Riveline D, Zamir E, Balaban NQ et al (2001) Focal contacts as mechanosensors: externally applied local mechanical force induces growth of focal contacts by an mDia1-dependent and ROCK-independent mechanism. J Cell Biol 153:1175–1185. doi:10.1083/jcb.153.6.1175
Rogers SL, Wiedemann U, Stuurman N, Vale RD (2003) Molecular requirements for actin-based lamella formation in Drosophila S2 cells. J Cell Biol 162:1079–1088. doi:10.1083/jcb.200303023
Romero S, Le Clainche C, Didry D et al (2004) Formin is a processive motor that requires profilin to accelerate actin assembly and associated ATP hydrolysis. Cell 119:419–429. doi:10.1016/j.cell.2004.09.039
Rotty JD, Wu C, Haynes EM et al (2015) Profilin-1 serves as a gatekeeper for actin assembly by Arp2/3-dependent and -independent pathways. Dev Cell 32:54–67. doi:10.1016/j.devcel.2014.10.026
Saarikangas J, Zhao H, Pykäläinen A et al (2009) Molecular mechanisms of membrane deformation by I-BAR domain proteins. Curr Biol 19:95–107. doi:10.1016/j.cub.2008.12.029
Saarikangas J, Zhao H, Lappalainen P (2010) Regulation of the actin cytoskeleton-plasma membrane interplay by phosphoinositides. Physiol Rev 90:259–289. doi:10.1152/physrev.00036.2009
Sagot I, Klee SK, Pellman D (2002) Yeast formins regulate cell polarity by controlling the assembly of actin cables. Nat Cell Biol 4:42–50. doi:10.1038/ncb719
Sandquist JC, Means AR (2008) The C-terminal tail region of nonmuscle myosin II directs isoform-specific distribution in migrating cells. Mol Biol Cell 19:5156–5167. doi:10.1091/mbc.E08-05-0533
Sanger JW, Sanger JM, Jockusch BM (1983) Differences in the stress fibers between fibroblasts and epithelial cells. J Cell Biol 96:961–969
Schirenbeck A, Bretschneider T, Arasada R et al (2005) The Diaphanous-related formin dDia2 is required for the formation and maintenance of filopodia. Nat Cell Biol 7:619–625. doi:10.1038/ncb1266
Schirenbeck A, Arasada R, Bretschneider T et al (2006) The bundling activity of vasodilator-stimulated phosphoprotein is required for filopodium formation. Proc Natl Acad Sci U S A 103:7694–7699. doi:10.1073/pnas.0511243103
Shimada A, Niwa H, Tsujita K et al (2007) Curved EFC/F-BAR-domain dimers are joined end to end into a filament for membrane invagination in endocytosis. Cell 129:761–772. doi:10.1016/j.cell.2007.03.040
Shutova MS, Spessott WA, Giraudo CG, Svitkina T (2014) Endogenous species of mammalian nonmuscle myosin IIA and IIB include activated monomers and heteropolymers. Curr Biol 24:1958–1968. doi:10.1016/j.cub.2014.07.070
Sinnar SA, Antoku S, Saffin J-M et al (2014) Capping protein is essential for cell migration in vivo and for filopodial morphology and dynamics. Mol Biol Cell 25:2152–2160. doi:10.1091/mbc.E13-12-0749
Skau CT, Plotnikov SV, Doyle AD, Waterman CM (2015) Inverted formin 2 in focal adhesions promotes dorsal stress fiber and fibrillar adhesion formation to drive extracellular matrix assembly. Proc Natl Acad Sci U S A 112:2447–2456. doi:10.1073/pnas.1505035112
Skoble J, Auerbuch V, Goley ED et al (2001) Pivotal role of VASP in Arp2/3 complex-mediated actin nucleation, actin branch-formation, and Listeria monocytogenes motility. J Cell Biol 155:89–100. doi:10.1083/jcb.200106061
Small JV, Celis JE (1978) Filament arrangements in negatively stained cultured cells: the organization of actin. Cytobiologie 16:308–325
Small JV, Rottner K, Kaverina I, Anderson KI (1998) Assembling an actin cytoskeleton for cell attachment and movement. Biochim Biophys Acta Mol Cell Res 1404:271–281. doi:10.1016/S0167-4889(98)00080-9
Suarez C, Carroll RT, Burke TA et al (2015) Profilin regulates F-actin network homeostasis by favoring formin over Arp2/3 complex. Dev Cell 32:43–53. doi:10.1016/j.devcel.2014.10.027
Suetsugu S, Murayama K, Sakamoto A et al (2006) The RAC binding domain/IRSp53-MIM homology domain of IRSp53 induces RAC-dependent membrane deformation. J Biol Chem 281:35347–35358. doi:10.1074/jbc.M606814200
Suraneni P, Rubinstein B, Unruh JR et al (2012) The Arp2/3 complex is required for lamellipodia extension and directional fibroblast cell migration. J Cell Biol 197:239–251. doi:10.1083/jcb.201112113
Svitkina TM, Borisy GG (1999) Arp2/3 complex and actin depolymerizing factor/cofilin in dendritic organization and treadmilling of actin filament array in Lamellipodia. J Cell Biol 145:1009–1026. doi:10.1083/jcb.145.5.1009
Svitkina TM, Verkhovsky AB, McQuade KM, Borisy GG (1997) Analysis of the actin-myosin II system in fish epidermal keratocytes: mechanism of cell body translocation. J Cell Biol 139:397–415. doi:10.1083/jcb.139.2.397
Svitkina TM, Bulanova EA, Chaga OY et al (2003) Mechanism of filopodia initiation by reorganization of a dendritic network. J Cell Biol 160:409–421. doi:10.1083/jcb.200210174
Taylor AC, Robbins E (1963) Observations on microextensions from the surface of isolated vertebrate cells. Dev Biol 7:660–673. doi:10.1016/0012-1606(63)90150-7
Tee YH, Shemesh T, Thiagarajan V et al (2015) Cellular chirality arising from the self-organization of the actin cytoskeleton. Nat Cell Biol 17:445–457. doi:10.1038/ncb3137
Tojkander S, Gateva G, Schevzov G et al (2011) A molecular pathway for myosin II recruitment to stress fibers. Curr Biol 21:539–550. doi:10.1016/j.cub.2011.03.007
Tojkander S, Gateva G, Lappalainen P (2012) Actin stress fibers – assembly, dynamics and biological roles. J Cell Sci 125:1855–1864. doi:10.1242/jcs.098087
Tojkander S, Gateva G, Husain A et al (2015) Generation of contractile actomyosin bundles depends on mechanosensitive actin filament assembly and disassembly. Elife 4:e06126
Tozluoğlu M, Tournier AL, Jenkins RP et al (2013) Matrix geometry determines optimal cancer cell migration strategy and modulates response to interventions. Nat Cell Biol 15:751–762. doi:10.1038/ncb2775
Tseng Y, Fedorov E, McCaffery JM et al (2001) Micromechanics and ultrastructure of actin filament networks crosslinked by human fascin: a comparison with alpha-actinin. J Mol Biol 310:351–366. doi:10.1006/jmbi.2001.4716
Türmer K, Orbán J, Gróf P, Nyitrai M (2015) FASCIN and alpha-actinin can regulate the conformation of actin filaments. Biochim Biophys Acta 1850:1855–1861. doi:10.1016/j.bbagen.2015.05.018
van den Dries K, Schwartz SL, Byars J et al (2013) Dual-color superresolution microscopy reveals nanoscale organization of mechanosensory podosomes. Mol Biol Cell 24:2112–2123. doi:10.1091/mbc.E12-12-0856
Vasioukhin V, Bauer C, Yin M, Fuchs E (2000) Directed actin polymerization is the driving force for epithelial cell-cell adhesion. Cell 100:209–219. doi:10.1016/S0092-8674(00)81559-7
Vicente-Manzanares M, Ma X, Adelstein RS, Horwitz R (2009) Non-muscle myosin II takes centre stage in cell adhesion and migration. Nat Rev Mol Cell Biol 10:778–790. doi:10.1038/nrm2786.Non-muscle
Vignjevic D, Kojima S, Aratyn Y et al (2006) Role of fascin in filopodial protrusion. J Cell Biol 174:863–875. doi:10.1083/jcb.200603013
Wang F, Harvey EV, Conti MA et al (2000) A conserved negatively charged amino acid modulates function in human nonmuscle myosin IIA. Biochemistry 39:5555–5560. doi:10.1021/bi000133x
Wang F, Kovacs M, Hu A et al (2003) Kinetic mechanism of non-muscle myosin IIB: functional adaptations for tension generation and maintenance. J Biol Chem 278:27439–27448. doi:10.1074/jbc.M302510200
Watanabe N, Mitchison TJ (2002) Single-molecule speckle analysis of actin filament turnover in lamellipodia. Science 295:1083–1086. doi:10.1126/science.1067470
Wiesner C, Faix J, Himmel M et al (2010) KIF5B and KIF3A/KIF3B kinesins drive MT1-MMP surface exposure, CD44 shedding, and extracellular matrix degradation in primary macrophages. Blood 116:1559–1569. doi:10.1182/blood-2009-12-257089
Wolf K, Mazo I, Leung H et al (2003) Compensation mechanism in tumor cell migration: mesenchymal-amoeboid transition after blocking of pericellular proteolysis. J Cell Biol 160:267–277. doi:10.1083/jcb.200209006
Wu C, Asokan SB, Berginski ME et al (2012) Arp2/3 is critical for lamellipodia and response to extracellular matrix cues but is dispensable for chemotaxis. Cell 148:973–987. doi:10.1016/j.cell.2011.12.034
Yang C, Svitkina T (2011) Filopodia initiation: focus on the Arp2/3 complex and formins. Cell Adh Migr 5:402–408. doi:10.4161/cam.5.5.16971
Yang C, Czech L, Gerboth S et al (2007) Novel roles of formin mDia2 in lamellipodia and filopodia formation in motile cells. PLoS Biol 5, e317. doi:10.1371/journal.pbio.0050317
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 SpringerInternationalPublishingSwitzerland
About this chapter
Cite this chapter
Lehtimäki, J., Hakala, M., Lappalainen, P. (2016). Actin Filament Structures in Migrating Cells. In: Jockusch, B. (eds) The Actin Cytoskeleton. Handbook of Experimental Pharmacology, vol 235. Springer, Cham. https://doi.org/10.1007/164_2016_28
Download citation
DOI: https://doi.org/10.1007/164_2016_28
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-46369-8
Online ISBN: 978-3-319-46371-1
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)