Extracellular signal-regulated kinase promotes rho-dependent focal adhesion formation by suppressing p190A RhoGAP

Molecular and Cellular Biology

Volumn 30, Issue 13, 2010, Pages 3233-3248

  Pullikuth, Ashok K ^a   Catling, Andrew D ^a  

^a LOUISIANA STATE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

FIBRONECTIN; GUANOSINE TRIPHOSPHATE; MITOGEN ACTIVATED PROTEIN KINASE; RHO KINASE;

ANIMAL CELL; ARTICLE; CARBOXY TERMINAL SEQUENCE; CELL ADHESION; CELL MIGRATION; ENZYME ACTIVITY; ENZYME PHOSPHORYLATION; NONHUMAN; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN LOCALIZATION; SIGNAL TRANSDUCTION;

ACTINS; AMINO ACID SEQUENCE; ANIMALS; BUTADIENES; CELL ADHESION; CELL LINE; ENZYME INHIBITORS; EXTRACELLULAR SIGNAL-REGULATED MAP KINASES; FIBRONECTINS; FOCAL ADHESIONS; HUMANS; MAP KINASE SIGNALING SYSTEM; MITOGEN-ACTIVATED PROTEIN KINASE KINASES; MOLECULAR SEQUENCE DATA; NITRILES; RATS; RECOMBINANT FUSION PROTEINS; REPRESSOR PROTEINS; RHO-ASSOCIATED KINASES; RHOA GTP-BINDING PROTEIN; RNA, SMALL INTERFERING; SEQUENCE ALIGNMENT; VINCULIN;

EID: 77953400433     PISSN: 02707306     EISSN: None     Source Type: Journal    
DOI: 10.1128/MCB.01178-09     Document Type: Article

References (90)

1. Aktories, K., and I. Just. 1995. In vitro ADP-ribosylation of Rho by bacterial ADP-ribosyltransferases. Methods Enzymol. 256:184-195.
2. Amano, M., K. Chihara, K. Kimura, Y. Fukata, N. Nakamura, Y. Matsuura, and K. Kaibuchi. 1997. Formation of actin stress fibers and focal adhesions enhanced by Rho-kinase. Science 275:1308-1311. (Pubitemid 27114159)
3. Amano, M., H. Mukai, Y. Ono, K. Chihara, T. Matsui, Y. Hamajima, K. Okawa, A. Iwamatsu, and K. Kaibuchi. 1996. Identification of a putative target for Rho as the serine-threonine kinase protein kinase N. Science 271:648-650. (Pubitemid 26052909)
4. Arthur, W. T., and K. Burridge. 2001. RhoA inactivation by p190RhoGAP regulates cell spreading and migration by promoting membrane protrusion and polarity. Mol. Biol. Cell 12:2711-2720.
5. Arthur, W. T., L. A. Petch, and K. Burridge. 2000. Integrin engagement suppresses RhoA activity via a c-Src-dependent mechanism. Curr. Biol. 10:719-722.
6. Bass, M. D., M. R. Morgan, K. A. Roach, J. Settleman, A. B. Goryachev, and M. J. Humphries. 2008. p190RhoGAP is the convergence point of adhesion signals from alpha 5 beta 1 integrin and syndecan-4. J. Cell Biol. 181:1013-1026.
7. Bhatt, A., I. Kaverina, C. Otey, and A. Huttenlocher. 2002. Regulation of focal complex composition and disassembly by the calcium-dependent protease calpain. J. Cell Sci. 115:3415-3425. (Pubitemid 34994031)
8. Bradley, W. D., S. E. Hernandez, J. Settleman, and A. J. Koleske. 2006. Integrin signaling through Arg activates p190RhoGAP by promoting its binding to p120RasGAP and recruitment to the membrane. Mol. Biol. Cell 17:4827-4836.
9. Brahmbhatt, A. A., and R. L. Klemke. 2003. ERK and RhoA differentially regulate pseudopodia growth and retraction during chemotaxis. J. Biol. Chem. 278:13016-13025.
10. Brouns, M. R., S. F. Matheson, K. Q. Hu, I. Delalle, V. S. Caviness, J. Silver, R. T. Bronson, and J. Settleman. 2000. The adhesion signaling molecule p190 RhoGAP is required for morphogenetic processes in neural development. Development 127:4891-4903.
11. Brouns, M. R., S. F. Matheson, and J. Settleman. 2001. p190 RhoGAP is the principal Src substrate in brain and regulates axon outgrowth, guidance and fasciculation. Nat. Cell Biol. 3:361-367.
12. Broussard, J. A., D. J. Webb, and I. Kaverina. 2008. Asymmetric focal adhesion disassembly in motile cells. Curr. Opin. Cell Biol. 20:85-90.
13. Burbelo, P. D., A. A. Finegold, C. A. Kozak, Y. Yamada, and H. Takami. 1998. Cloning, genomic organization and chromosomal assignment of the mouse p190-B gene. Biochim. Biophys. Acta 1443:203-210.
14. Burbelo, P. D., S. Miyamoto, A. Utani, S. Brill, K. M. Yamada, A. Hall, and Y. Yamada. 1995. p190-B, a new member of the Rho GAP family, and Rho are induced to cluster after integrin cross-linking. J. Biol. Chem. 270:30919-30926.
15. Carragher, N. O., M. A. Westhoff, V. J. Fincham, M. D. Schaller, and M. C. Frame. 2003. A novel role for FAK as a protease-targeting adaptor protein: regulation by p42 ERK and Src. Curr. Biol. 13:1442-1450.
16. Catling, A. D., H. J. Schaeffer, C. W. Reuter, G. R. Reddy, and M. J. Weber. 1995. A proline-rich sequence unique to MEK1 and MEK2 is required for raf binding and regulates MEK function. Mol. Cell. Biol. 15:5214-5225.
17. Chang, J. H., S. Gill, J. Settleman, and S. J. Parsons. 1995. c-Src regulates the simultaneous rearrangement of actin cytoskeleton, p190RhoGAP, and p120RasGAP following epidermal growth factor stimulation. J. Cell Biol. 130:355-368.
18. Chen, B. H., J. T. Tzen, A. R. Bresnick, and H. C. Chen. 2002. Roles of Rho-associated kinase and myosin light chain kinase in morphological and migratory defects of focal adhesion kinase-null cells. J. Biol. Chem. 277: 33857-33863.
19. Chen, J. C., S. Zhuang, T. H. Nguyen, G. R. Boss, and R. B. Pilz. 2003. Oncogenic Ras leads to Rho activation by activating the mitogen-activated protein kinase pathway and decreasing Rho-GTPase-activating protein activity. J. Biol. Chem. 278:2807-2818.
20. Chen, Q., M. S. Kinch, T. H. Lin, K. Burridge, and R. L. Juliano. 1994. Integrin-mediated cell adhesion activates mitogen-activated protein kinases. J. Biol. Chem. 269:26602-26605.
21. Cheresh, D. A., J. Leng, and R. L. Klemke. 1999. Regulation of cell contraction and membrane ruffling by distinct signals in migratory cells. J. Cell Biol. 146:1107-1116.
22. Chrzanowska-Wodnicka, M., and K. Burridge. 1996. Rho-stimulated contractility drives the formation of stress fibers and focal adhesions. J. Cell Biol. 133:1403-1415. (Pubitemid 26192339)
23. Clark-Lewis, I., J. S. Sanghera, and S. L. Pelech. 1991. Definition of a consensus sequence for peptide substrate recognition by p44mpk, the meiosis-activated myelin basic protein kinase. J. Biol. Chem. 266:15180-15184.
24. Cox, E. A., S. K. Sastry, and A. Huttenlocher. 2001. Integrin-mediated adhesion regulates cell polarity and membrane protrusion through the Rho family of GTPases. Mol. Biol. Cell 12:265-277.
25. Cuevas, B. D., A. N. Abell, J. A. Witowsky, T. Yujiri, N. L. Johnson, K. Kesavan, M. Ware, P. L. Jones, S. A. Weed, R. L. DeBiasi, Y. Oka, K. L. Tyler, and G. L. Johnson. 2003. MEKK1 regulates calpain-dependent proteolysis of focal adhesion proteins for rear-end detachment of migrating fibroblasts. EMBO J. 22:3346-3355.
26. Eblen, S. T., J. K. Slack-Davis, A. Tarcsafalvi, J. T. Parsons, M. J. Weber, and A. D. Catling. 2004. Mitogen-activated protein kinase feedback phosphorylation regulates MEK1 complex formation and activation during cellular adhesion. Mol. Cell. Biol. 24:2308-2317.
27. Ellis, C., M. Moran, F. McCormick, and T. Pawson. 1990. Phosphorylation of GAP and GAP-associated proteins by transforming and mitogenic tyrosine kinases. Nature 343:377-381.
28. Etienne-Manneville, S., and A. Hall. 2003. Cdc42 regulates GSK-3beta and adenomatous polyposis coli to control cell polarity. Nature 421:753-756. (Pubitemid 36227627)
29. Favata, M. F., K. Y. Horiuchi, E. J. Manos, A. J. Daulerio, D. A. Stradley, W. S. Feeser, D. E. Van Dyk, W. J. Pitts, R. A. Earl, F. Hobbs, R. A. Copeland, R. L. Magolda, P. A. Scherle, and J. M. Trzaskos. 1998. Identification of a novel inhibitor of mitogen-activated protein kinase kinase. J. Biol. Chem. 273:18623-18632.
30. Feng, J., M. Ito, K. Ichikawa, N. Isaka, M. Nishikawa, D. J. Hartshorne, and T. Nakano. 1999. Inhibitory phosphorylation site for Rho-associated kinase on smooth muscle myosin phosphatase. J. Biol. Chem. 274:37385-37390.
31. Fincham, V. J., A. Chudleigh, and M. C. Frame. 1999. Regulation of p190 Rho-GAP by v-Src is linked to cytoskeletal disruption during transformation. J. Cell Sci. 112:947-956.
32. Fincham, V. J., M. James, M. C. Frame, and S. J. Winder. 2000. Active ERK/MAP kinase is targeted to newly forming cell-matrix adhesions by integrin engagement and v-Src. EMBO J. 19:2911-2923.
33. Franco, S. J., M. A. Rodgers, B. J. Perrin, J. Han, D. A. Bennin, D. R. Critchley, and A. Huttenlocher. 2004. Calpain-mediated proteolysis of talin regulates adhesion dynamics. Nat. Cell Biol. 6:977-983.
34. Garcia-Mata, R., K. Wennerberg, W. T. Arthur, N. K. Noren, S. M. Ellerbroek, and K. Burridge. 2006. Analysis of activated GAPs and GEFs in cell lysates. Methods Enzymol. 406:425-437.
35. Geiger, B., and A. Bershadsky. 2001. Assembly and mechanosensory function of focal contacts. Curr. Opin. Cell Biol. 13:584-592.
36. Glading, A., R. J. Bodnar, I. J. Reynolds, H. Shiraha, L. Satish, D. A. Potter, H. C. Blair, and A. Wells. 2004. Epidermal growth factor activates m-calpain (calpain II), at least in part, by extracellular signal-regulated kinase-mediated phosphorylation. Mol. Cell. Biol. 24:2499-2512.
37. Glading, A., P. Chang, D. A. Lauffenburger, and A. Wells. 2000. Epidermal growth factor receptor activation of calpain is required for fibroblast motility and occurs via an ERK/MAP kinase signaling pathway. J. Biol. Chem. 275: 2390-2398.
38. Hall, A., and C. D. Nobes. 2000. Rho GTPases: molecular switches that control the organization and dynamics of the actin cytoskeleton. Philos Trans. R. Soc. Lond. B Biol. Sci. 355:965-970.
39. Haskell, M. D., A. L. Nickles, J. M. Agati, L. Su, B. D. Dukes, and S. J. Parsons. 2001. Phosphorylation of p190 on Tyr1105 by c-Src is necessary but not sufficient for EGF-induced actin disassembly in C3H10T1/2 fibroblasts. J. Cell Sci. 114:1699-1708.
40. Haskell, M. D., J. K. Slack, J. T. Parsons, and S. J. Parsons. 2001. c-Src tyrosine phosphorylation of epidermal growth factor receptor, P190 RhoGAP, and focal adhesion kinase regulates diverse cellular processes. Chem. Rev. 101:2425-2440.
41. Heckman, B. M., G. Chakravarty, T. Vargo-Gogola, M. Gonzales-Rimbau, D. L. Hadsell, A. V. Lee, J. Settleman, and J. M. Rosen. 2007. Crosstalk between the p190-B RhoGAP and IGF signaling pathways is required for embryonic mammary bud development. Dev. Biol. 309:137-149.
42. Hernandez, S. E., J. Settleman, and A. J. Koleske. 2004. Adhesion-dependent regulation of p190RhoGAP in the developing brain by the Abl-related gene tyrosine kinase. Curr. Biol. 14:691-696.
43. Ichikawa, K., M. Ito, and D. J. Hartshorne. 1996. Phosphorylation of the large subunit of myosin phosphatase and inhibition of phosphatase activity. J. Biol. Chem. 271:4733-4740.
44. Ishibe, S., D. Joly, X. Zhu, and L. G. Cantley. 2003. Phosphorylation-dependent paxillin-ERK association mediates hepatocyte growth factor-stimulated epithelial morphogenesis. Mol. Cell 12:1275-1285.
45. Ishizaki, T., M. Uehata, I. Tamechika, J. Keel, K. Nonomura, M. Maekawa, and S. Narumiya. 2000. Pharmacological properties of Y-27632, a specific inhibitor of rho-associated kinases. Mol. Pharmacol. 57:976-983.
46. Jacobs, D., D. Glossip, H. Xing, A. J. Muslin, and K. Kornfeld. 1999. Multiple docking sites on substrate proteins form a modular system that mediates recognition by ERK MAP kinase. Genes Dev. 13:163-175.
47. Jiang, W., M. Betson, R. Mulloy, R. Foster, M. Levay, E. Ligeti, and J. Settleman. 2008. p190A RhoGAP is a glycogen synthase kinase-3-beta substrate required for polarized cell migration. J. Biol. Chem. 283:20978-20988.
48. Jo, M., K. S. Thomas, A. V. Somlyo, A. P. Somlyo, and S. L. Gonias. 2002. Cooperativity between the Ras-ERK and Rho-Rho kinase pathways in urokinase-type plasminogen activator-stimulated cell migration. J. Biol. Chem. 277:12479-12485.
49. Kawano, Y., Y. Fukata, N. Oshiro, M. Amano, T. Nakamura, M. Ito, F. Matsumura, M. Inagaki, and K. Kaibuchi. 1999. Phosphorylation of myosin-binding subunit (MBS) of myosin phosphatase by Rho-kinase in vivo. J. Cell Biol. 147:1023-1038.
50. Klemke, R. L., S. Cai, A. L. Giannini, P. J. Gallagher, P. de Lanerolle, and D. A. Cheresh. 1997. Regulation of cell motility by mitogen-activated protein kinase. J. Cell Biol. 137:481-492. (Pubitemid 27181299)
51. Koch, C. A., D. Anderson, M. F. Moran, C. Ellis, and T. Pawson. 1991. SH2 and SH3 domains: elements that control interactions of cytoplasmic signaling proteins. Science 252:668-674. (Pubitemid 21916987)
52. Kulkarni, S., D. E. Goll, and J. E. Fox. 2002. Calpain cleaves RhoA generating a dominant-negative form that inhibits integrin-induced actin filament assembly and cell spreading. J. Biol. Chem. 277:24435-24441.
53. Kulkarni, S. V., G. Gish, P. van der Geer, M. Henkemeyer, and T. Pawson. 2000. Role of p120 Ras-GAP in directed cell movement. J. Cell Biol. 149: 457-470.
54. Kurokawa, K., and M. Matsuda. 2005. Localized RhoA activation as a requirement for the induction of membrane ruffling. Mol. Biol. Cell 16:4294-4303.
55. Machesky, L. M., and A. Hall. 1997. Role of actin polymerization and adhesion to extracellular matrix in Rac- and Rho-induced cytoskeletal reorganization. J. Cell Biol. 138:913-926.
56. Nakahara, H., S. C. Mueller, M. Nomizu, Y. Yamada, Y. Yeh, and W. T. Chen. 1998. Activation of beta1 integrin signaling stimulates tyrosine phosphorylation of p190RhoGAP and membrane-protrusive activities at invadopodia. J. Biol. Chem. 273:9-12.
57. Nobes, C. D., and A. Hall. 1999. Rho GTPases control polarity, protrusion, and adhesion during cell movement. J. Cell Biol. 144:1235-1244. (Pubitemid 29157301)
58. Nobes, C. D., and A. Hall. 1995. Rho, rac, and cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia. Cell 81:53-62.
59. Noren, N. K., W. T. Arthur, and K. Burridge. 2003. Cadherin engagement inhibits RhoA via p190RhoGAP. J. Biol. Chem. 278:13615-13618.
60. Obenauer, J. C., L. C. Cantley, and M. B. Yaffe. 2003. Scansite 2.0: proteome-wide prediction of cell signaling interactions using short sequence motifs. Nucleic Acids Res. 31:3635-3641.
61. Peacock, J. G., A. L. Miller, W. D. Bradley, O. C. Rodriguez, D. J. Webb, and A. J. Koleske. 2007. The Abl-related gene tyrosine kinase acts through p190RhoGAP to inhibit actomyosin contractility and regulate focal adhesion dynamics upon adhesion to fibronectin. Mol. Biol. Cell 18:3860-3872.
62. Pertz, O., L. Hodgson, R. L. Klemke, and K. M. Hahn. 2006. Spatiotemporal dynamics of RhoA activity in migrating cells. Nature 440:1069-1072.
63. Price, L. S., J. Leng, M. A. Schwartz, and G. M. Bokoch. 1998. Activation of Rac and Cdc42 by integrins mediates cell spreading. Mol. Biol. Cell 9:1863-1871.
64. Pullikuth, A., E. McKinnon, H. J. Schaeffer, and A. D. Catling. 2005. The MEK1 scaffolding protein MP1 regulates cell spreading by integrating PAK1 and Rho signals. Mol. Cell. Biol. 25:5119-5133.
65. Ren, X. D., W. B. Kiosses, and M. A. Schwartz. 1999. Regulation of the small GTP-binding protein Rho by cell adhesion and the cytoskeleton. EMBO J. 18:578-585. (Pubitemid 29057242)
66. Ren, X. D., and M. A. Schwartz. 2000. Determination of GTP loading on Rho. Methods Enzymol. 325:264-272.
67. Ridley, A. 2000. Rho GTPases. Integrating integrin signaling. J. Cell Biol. 150:F107-F109.
68. Ridley, A. J., and A. Hall. 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.
69. Ridley, A. J., M. A. Schwartz, K. Burridge, R. A. Firtel, M. H. Ginsberg, G. Borisy, J. T. Parsons, and A. R. Horwitz. 2003. Cell migration: integrating signals from front to back. Science 302:1704-1709.
70. Ridley, A. J., A. J. Self, F. Kasmi, H. F. Paterson, A. Hall, C. J. Marshall, and C. Ellis. 1993. rho family GTPase activating proteins p190, bcr and rhoGAP show distinct specificities in vitro and in vivo. EMBO J. 12:5151-5160.
71. Roof, R. W., M. D. Haskell, B. D. Dukes, N. Sherman, M. Kinter, and S. J. Parsons. 1998. Phosphotyrosine (p-Tyr)-dependent and -independent mechanisms of p190 RhoGAP-p120 RasGAP interaction: Tyr 1105 of p190, a substrate for c-Src, is the sole p-Tyr mediator of complex formation. Mol. Cell. Biol. 18:7052-7063.
72. Schaeffer, H. J., A. D. Catling, S. T. Eblen, L. S. Collier, A. Krauss, and M. J. Weber. 1998. MP1: a MEK binding partner that enhances enzymatic activation of the MAP kinase cascade. Science 281:1668-1671.
73. Schagger, H., and G. von Jagow. 1987. Tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis for the separation of proteins in the range from 1 to 100 kDa. Anal. Biochem. 166:368-379.
74. Settleman, J., V. Narasimhan, L. C. Foster, and R. A. Weinberg. 1992. Molecular cloning of cDNAs encoding the GAP-associated protein p190: implications for a signaling pathway from ras to the nucleus. Cell 69:539-549.
75. Sharma, S. V. 1998. Rapid recruitment of p120RasGAP and its associated protein, p190RhoGAP, to the cytoskeleton during integrin mediated cell-substrate interaction. Oncogene 17:271-281.
76. Slack-Davis, J. K., S. T. Eblen, M. Zecevic, S. A. Boerner, A. Tarcsafalvi, H. B. Diaz, M. S. Marshall, M. J. Weber, J. T. Parsons, and A. D. Catling. 2003. PAK1 phosphorylation of MEK1 regulates fibronectin-stimulated MAPK activation. J. Cell Biol. 162:281-291.
77. Sordella, R., M. Classon, K. Q. Hu, S. F. Matheson, M. R. Brouns, B. Fine, L. Zhang, H. Takami, Y. Yamada, and J. Settleman. 2002. Modulation of CREB activity by the Rho GTPase regulates cell and organism size during mouse embryonic development. Dev. Cell 2:553-565.
78. Sordella, R., W. Jiang, G. C. Chen, M. Curto, and J. Settleman. 2003. Modulation of Rho GTPase signaling regulates a switch between adipogenesis and myogenesis. Cell 113:147-158.
79. Stahle, M., C. Veit, U. Bachfischer, K. Schierling, B. Skripczynski, A. Hall, P. Gierschik, and K. Giehl. 2003. Mechanisms in LPA-induced tumor cell migration: critical role of phosphorylated ERK. J. Cell Sci. 116:3835-3846. (Pubitemid 37185312)
80. Su, L., J. M. Agati, and S. J. Parsons. 2003. p190RhoGAP is cell cycle regulated and affects cytokinesis. J. Cell Biol. 163:571-582. (Pubitemid 37429870)
81. Sumi, T., K. Matsumoto, and T. Nakamura. 2001. Specific activation of LIM kinase 2 via phosphorylation of threonine 505 by ROCK, a Rho-dependent protein kinase. J. Biol. Chem. 276:670-676.
82. Sumi, T., K. Matsumoto, Y. Takai, and T. Nakamura. 1999. Cofilin phosphorylation and actin cytoskeletal dynamics regulated by rho- and Cdc42-activated LIM-kinase 2. J. Cell Biol. 147:1519-1532. (Pubitemid 30027406)
83. Tanoue, T., M. Adachi, T. Moriguchi, and E. Nishida. 2000. A conserved docking motif in MAP kinases common to substrates, activators and regulators. Nat. Cell Biol. 2:110-116.
84. Tsubouchi, A., J. Sakakura, R. Yagi, Y. Mazaki, E. Schaefer, H. Yano, and H. Sabe. 2002. Localized suppression of RhoA activity by Tyr31/118- phosphorylated paxillin in cell adhesion and migration. J. Cell Biol. 159:673-683.
85. Vomastek, T., M. P. Iwanicki, H. J. Schaeffer, A. Tarcsafalvi, J. T. Parsons, and M. J. Weber. 2007. RACK1 targets the extracellular signal-regulated kinase/mitogen-activated protein kinase pathway to link integrin engagement with focal adhesion disassembly and cell motility. Mol. Cell. Biol. 27:8296-8305.
86. Webb, D. J., K. Donais, L. A. Whitmore, S. M. Thomas, C. E. Turner, J. T. Parsons, and A. F. Horwitz. 2004. FAK-Src signalling through paxillin, ERK and MLCK regulates adhesion disassembly. Nat. Cell Biol. 6:154-161.
87. Worthylake, R. A., and K. Burridge. 2003. RhoA and ROCK promote migration by limiting membrane protrusions. J. Biol. Chem. 278:13578-13584.
88. Yang, N., O. Higuchi, K. Ohashi, K. Nagata, A. Wada, K. Kangawa, E. Nishida, and K. Mizuno. 1998. Cofilin phosphorylation by LIM-kinase 1 and its role in Rac-mediated actin reorganization. Nature 393:809-812. (Pubitemid 28299495)
89. Yin, G., Q. Zheng, C. Yan, and B. C. Berk. 2005. GIT1 is a scaffold for ERK1/2 activation in focal adhesions. J. Biol. Chem. 280:27705-27712.
90. Zaidel-Bar, R., C. Ballestrem, Z. Kam, and B. Geiger. 2003. Early molecular events in the assembly of matrix adhesions at the leading edge of migrating cells. J. Cell Sci. 116:4605-4613.