Structural and mechanical functions of integrins

Biophysical Reviews

Volumn 6, Issue 2, 2014, Pages 203-213

  Anderson, Luke R ^a   Owens, Thomas W ^a   Naylor, Matthew J ^a  

^a UNIVERSITY OF SYDNEY   (Australia)

Author keywords

Extracellular matrix; Focal adhesion; Inside out signalling; Integrins; Migration; Outside in signalling

Indexed keywords

ALPHA ACTININ; BETA1 INTEGRIN; CD18 ANTIGEN; CORTACTIN; CYCLIN D1; DYNAMIN; FIBRINOGEN; FILAMIN; FOCAL ADHESION KINASE; GELSOLIN; INTEGRIN; INTEGRIN LINKED KINASE; INTERCELLULAR ADHESION MOLECULE 1; KINDLIN; LAMININ; MITOGEN ACTIVATED PROTEIN KINASE; PAXILLIN; PEPTIDES AND PROTEINS; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; PROTEIN TYROSINE KINASE; RAC1 PROTEIN; TALIN; TENSIN; UNCLASSIFIED DRUG; VINCULIN;

BINDING AFFINITY; CELL ADHESION; CELL CYCLE PROGRESSION; CELL FATE; CELL INTERACTION; CELL MIGRATION; CELL SURVIVAL; EXTRACELLULAR MATRIX; GLYCOCALYX; HUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; REVIEW; SIGNAL TRANSDUCTION; STRUCTURE ACTIVITY RELATION;

EID: 84900314545     PISSN: 18672450     EISSN: 18672469     Source Type: Journal    
DOI: 10.1007/s12551-013-0124-0     Document Type: Review

References (134)

1. Abram C, Lowell C (2009) The ins and outs of leukocyte integrin signaling. Annu Rev Immunol 27: 339-362.
2. Adair B, Xiong J-P, Maddock C, Goodman S, Arnaout M, Yeager M (2005) Three-dimensional EM structure of the ectodomain of integrin {alpha}V{beta}3 in a complex with fibronectin. J Cell Biol 168: 1109-1118.
3. Ahmed N, Niu J, Dorahy D, Gu X, Andrews S, Meldrum C et al (2002) Direct integrin alphavbeta6-ERK binding: implications for tumour growth. Oncogene 21: 1370-1380.
4. Akhtar N, Marlow R, Lambert E, Schatzmann F, Lowe ET, Cheung J et al (2009) Molecular dissection of integrin signalling proteins in the control of mammary epithelial development and differentiation. Development 136: 1019-1027.
5. Arias-Salgado E, Lizano S, Sarkar S, Brugge J, Ginsberg M, Shattil S (2003) Src kinase activation by direct interaction with the integrin beta cytoplasmic domain. Proc Natl Acad Sci USA 100: 13298-13302.
6. Arias-Salgado E, Lizano S, Shattil S, Ginsberg M (2005) Specification of the direction of adhesive signaling by the integrin beta cytoplasmic domain. J Biol Chem 280: 29699-29707.
7. Arnaout M, Mahalingam B, Xiong JP (2005) Integrin structure, allostery, and bidirectional signaling. Annu Rev Cell Dev Biol 21: 381-791.
8. Arnaout M, Goodman S, Xiong J-P (2007) Structure and mechanics of integrin-based cell adhesion. Curr Opin Cell Biol 19: 495-507.
9. Atilgan E, Ovryn B (2009) Nucleation and growth of integrin adhesions. Biophys J 96: 3555-3572.
10. Baker R, Koretzky G (2008) Regulation of T cell integrin function by adapter proteins. Immunol Res 42: 132-176.
11. Beglova N, Blacklow S, Takagi J, Springer T (2002) Cysteine-rich module structure reveals a fulcrum for integrin rearrangement upon activation. Nat Struct Biol 9: 282-287.
12. Bell G (1978) Models for the specific adhesion of cells to cells. Science (New York, NY) 200: 618-627.
13. Boettiger D (2012) Mechanical control of integrin-mediated adhesion and signaling. Curr Opin Cell Biol 24: 592-599.
14. Boettiger D, Wehrle-Haller B (2010) Integrin and glycocalyx mediated contributions to cell adhesion identified by single cell force spectroscopy. J Phys 22: 194101.
15. Bouvard D, Pouwels J, De Franceschi N, Ivaska J (2013) Integrin inactivators: balancing cellular functions in vitro and in vivo. Nat Rev Mol Cell Biol 14: 430-442.
16. Brunner M, Millon-Frémillon A, Chevalier G, Nakchbandi IA, Mosher D, Block MR et al (2011) Osteoblast mineralization requires β1 integrin/ICAP-1-dependent fibronectin deposition. J Cell Biol 194: 307-322.
17. Bunch T (2010) Integrin alphaIIbbeta3 activation in Chinese hamster ovary cells and platelets increases clustering rather than affinity. J Biol Chem 285: 1841-1849.
18. Calderwood D, Zent R, Grant R, Rees D, Hynes R, Ginsberg M (1999) The Talin head domain binds to integrin beta subunit cytoplasmic tails and regulates integrin activation. J Biol Chem 274: 28071-28074.
19. Calderwood D, Huttenlocher A, Kiosses W, Rose D, Woodside D, Schwartz M et al (2001) Increased filamin binding to beta-integrin cytoplasmic domains inhibits cell migration. Nat Cell Biol 3: 1060-1068.
20. Calderwood D, Yan B, de Pereda J, Alvarez B, Fujioka Y, Liddington R et al (2002) The phosphotyrosine binding-like domain of talin activates integrins. J Biol Chem 277: 21749-21758.
21. Calderwood D, Fujioka Y, de Pereda J, García-Alvarez B, Nakamoto T, Margolis B et al (2003) Integrin beta cytoplasmic domain interactions with phosphotyrosine-binding domains: a structural prototype for diversity in integrin signaling. Proc Natl Acad Sci USA 100: 2272-2277.
22. Carter W, Kaur P, Gil S, Gahr P, Wayner E (1990) Distinct functions for integrins alpha 3 beta 1 in focal adhesions and alpha 6 beta 4/bullous pemphigoid antigen in a new stable anchoring contact (SAC) of keratinocytes: relation to hemidesmosomes. J Cell Biol 111: 3141-3154.
23. Chao W-T, Kunz J (2009) Focal adhesion disassembly requires clathrin-dependent endocytosis of integrins. FEBS Lett 583: 1337-1343.
24. Chao W-T, Ashcroft F, Daquinag A, Vadakkan T, Wei Z, Zhang P et al (2010a) Type I phosphatidylinositol phosphate kinase beta regulates focal adhesion disassembly by promoting beta1 integrin endocytosis. Mol Cell Biol 30: 4463-4479.
25. Chao W-T, Daquinag A, Ashcroft F, Kunz J (2010b) Type I PIPK-alpha regulates directed cell migration by modulating Rac1 plasma membrane targeting and activation. J Cell Biol 190: 247-262.
26. Chellaiah M, Kizer N, Silva M, Alvarez U, Kwiatkowski D, Hruska K (2000) Gelsolin deficiency blocks podosome assembly and produces increased bone mass and strength. J Cell Biol 148: 665-678.
27. Chen H, Guan J (1994) Association of focal adhesion kinase with its potential substrate phosphatidylinositol 3-kinase. Proc Natl Acad Sci USA 91: 10148-10152.
28. Chen L, Bailey D, Fernandez-Valle C (2000) Association of beta 1 integrin with focal adhesion kinase and paxillin in differentiating Schwann cells. J Neurosci 20: 3776-3784.
29. Chen J, Yang W, Kim M, Carman C, Springer T (2006) Regulation of outside-in signaling and affinity by the beta2 I domain of integrin alphaLbeta2. Proc Natl Acad Sci USA 103: 13062-13067.
30. Chhabra E, Higgs H (2007) The many faces of actin: matching assembly factors with cellular structures. Nat Cell Biol 9: 1110-1121.
31. Choi C, Vicente-Manzanares M, Zareno J, Whitmore L, Mogilner A, Horwitz A (2008) Actin and alpha-actinin orchestrate the assembly and maturation of nascent adhesions in a myosin II motor-independent manner. Nat Cell Biol 10: 1039-1050.
32. Choi C, Zareno J, Digman M, Gratton E, Horwitz A (2011) Cross-correlated fluctuation analysis reveals phosphorylation-regulated paxillin-FAK complexes in nascent adhesions. Biophys J 100: 583-592.
33. Cluzel C, Saltel F, Lussi J, Paulhe F, Imhof B, Wehrle-Haller B (2005) The mechanisms and dynamics of (alpha)v(beta)3 integrin clustering in living cells. J Cell Biol 171: 383-392.
34. Cox S, Baur P, Haenelt B (1977) Retention of the glycocalyx after cell detachment by EGTA. J Histochem Cytochem 25: 1368-1372.
35. DiPersio C, Hodivala-Dilke K, Jaenisch R, Kreidberg J, Hynes R (1997) alpha3beta1 Integrin is required for normal development of the epidermal basement membrane. J Cell Biol 137: 729-742.
36. Eliceiri B, Puente X, Hood J, Stupack D, Schlaepfer D, Huang X et al (2002) Src-mediated coupling of focal adhesion kinase to integrin alpha(v)beta5 in vascular endothelial growth factor signaling. J Cell Biol 157: 149-160.
37. Ezratty E, Bertaux C, Marcantonio E, Gundersen G (2009) Clathrin mediates integrin endocytosis for focal adhesion disassembly in migrating cells. J Cell Biol 187: 733-747.
38. Fagerholm S, Hilden T, Nurmi S, Gahmberg C (2005) Specific integrin alpha and beta chain phosphorylations regulate LFA-1 activation through affinity-dependent and -independent mechanisms. J Cell Biol 171: 705-715.
39. Fournier HN, Dupe-Manet S, Bouvard D, Lacombe ML, Marie C, Block MR et al (2002) Integrin cytoplasmic domain-associated protein 1alpha (ICAP-1alpha) interacts directly with the metastasis suppressor nm23-H2, and both proteins are targeted to newly formed cell adhesion sites upon integrin engagement. J Biol Chem 277: 20895-20902.
40. Fournier M, Sauser R, Ambrosi D, Meister J-J, Verkhovsky A (2010) Force transmission in migrating cells. J Cell Biol 188: 287-297.
41. Freed E, Gailit J, van der Geer P, Ruoslahti E, Hunter T (1989) A novel integrin beta subunit is associated with the vitronectin receptor alpha subunit (alpha v) in a human osteosarcoma cell line and is a substrate for protein kinase C. EMBO J 8: 2955-2965.
42. Galbraith C, Yamada K, Galbraith J (2007) Polymerizing actin fibers position integrins primed to probe for adhesion sites. Science (New York) 315: 992-995.
43. Geiger B, Bershadsky A, Pankov R, Yamada K (2001) Transmembrane crosstalk between the extracellular matrix-cytoskeleton crosstalk. Nat Rev Mol Cell Biol 2: 793-805.
44. Goksoy E, Ma Y-Q, Wang X, Kong X, Perera D, Plow E et al (2008) Structural basis for the autoinhibition of talin in regulating integrin activation. Mol Cell 31: 124-133.
45. Gottschalk K-E (2005) A coiled-coil structure of the alphaIIbbeta3 integrin transmembrane and cytoplasmic domains in its resting state. Structure (London) 13: 703-712.
46. Gotwals P, Fessler L, Wehrli M, Hynes R (1994) Drosophila PS1 integrin is a laminin receptor and differs in ligand specificity from PS2. Proc Natl Acad Sci USA 91: 11447-11451.
47. Hagel M, George EL, Kim A, Tamimi R, Opitz SL, Turner CE et al (2002) The adaptor protein paxillin is essential for normal development in the mouse and is a critical transducer of fibronectin signaling. Mol Cell Biol 22: 901-915.
48. Han D, Rodriguez L, Guan J (2001) Identification of a novel interaction between integrin beta1 and 14-3-3beta. Oncogene 20: 346-357.
49. Hannigan GE, Leung-Hagesteijn C, Fitz-Gibbon L, Coppolino MG, Radeva G, Filmus J et al (1996) Regulation of cell adhesion and anchorage-dependent growth by a new beta 1-integrin-linked protein kinase. Nature 379: 91-96.
50. Heino J (2007) The collagen family members as cell adhesion proteins. Bioessays 29: 1001-1010.
51. Heino J, Ignotz R, Hemler M, Crouse C, Massagué J (1989) Regulation of cell adhesion receptors by transforming growth factor-beta. Concomitant regulation of integrins that share a common beta 1 subunit. J Biol Chem 264: 380-388.
52. Hibbs M, Jakes S, Stacker S, Wallace R, Springer T (1991) The cytoplasmic domain of the integrin lymphocyte function-associated antigen 1 beta subunit: sites required for binding to intercellular adhesion molecule 1 and the phorbol ester-stimulated phosphorylation site. J Exp Med 174: 1227-1238.
53. Hodivala-Dilke K, DiPersio C, Kreidberg J, Hynes R (1998) Novel roles for alpha3beta1 integrin as a regulator of cytoskeletal assembly and as a trans-dominant inhibitor of integrin receptor function in mouse keratinocytes. J Cell Biol 142: 1357-1369.
54. Huang C, Zang Q, Takagi J, Springer T (2000) Structural and functional studies with antibodies to the integrin beta 2 subunit. A model for the I-like domain. J Biol Chem 275: 21514-21524.
55. Huhtala M, Heino J, Casciari D, de Luise A, Johnson M (2005) Integrin evolution: insights from ascidian and teleost fish genomes. Matrix Biol 24: 83-95.
56. Humphries J, Byron A, Humphries M (2006) Integrin ligands at a glance. J Cell Sci 119: 3901-3904.
57. Hynes R (1992) Integrins: versatility, modulation, and signaling in cell adhesion. Cell 69: 11-25.
58. Hynes RO (2002) Integrins: bidirectional, allosteric signaling machines. Cell 110: 673-687.
59. Ilic D, Furuta Y, Kanazawa S, Takeda N, Sobue K, Nakatsuji N et al (1995) Reduced cell motility and enhanced focal adhesion contact formation in cells from FAK-deficient mice. Nature 377: 539-544.
60. Ito S (1969) Structure and function of the glycocalyx. Fed Proc 28: 12-25.
61. Jaffe A, Hall A (2005) Rho GTPases: biochemistry and biology. Annu Rev Cell Dev Biol 21: 247-269.
62. Jiang G, Giannone G, Critchley D, Fukumoto E, Sheetz M (2003) Two-piconewton slip bond between fibronectin and the cytoskeleton depends on talin. Nature 424: 334-337.
63. Johnson M, Lu N, Denessiouk K, Heino J, Gullberg D (2009) Integrins during evolution: evolutionary trees and model organisms. Biochim Biophys Acta 1788: 779-789.
64. Kano Y, Katoh K, Masuda M, Fujiwara K (1996) Macromolecular composition of stress fiber-plasma membrane attachment sites in endothelial cells in situ. Circ Res 79: 1000-1006.
65. Kim M, Carman C, Springer T (2003) Bidirectional transmembrane signaling by cytoplasmic domain separation in integrins. Science (New York) 301: 1720-1725.
66. Kiosses W, Shattil S, Pampori N, Schwartz M (2001) Rac recruits high-affinity integrin alphavbeta3 to lamellipodia in endothelial cell migration. Nat Cell Biol 3: 316-320.
67. Kirk R, Sanderson M, Lerea K (2000) Threonine phosphorylation of the beta 3 integrin cytoplasmic tail, at a site recognized by PDK1 and Akt/PKB in vitro, regulates Shc binding. J Biol Chem 275: 30901-30906.
68. Kloeker S, Major M, Calderwood D, Ginsberg M, Jones D, Beckerle M (2004) The Kindler syndrome protein is regulated by transforming growth factor-beta and involved in integrin-mediated adhesion. J Biol Chem 279: 6824-6833.
69. Kong F, García A, Mould A, Humphries M, Zhu C (2009) Demonstration of catch bonds between an integrin and its ligand. J Cell Biol 185: 1275-1284.
70. Kuo J-C, Han X, Hsiao C-T, Yates J, Waterman C (2011) Analysis of the myosin-II-responsive focal adhesion proteome reveals a role for β-Pix in negative regulation of focal adhesion maturation. Nat Cell Biol 13: 383-393.
71. Laurie G, Leblond C, Martin G (1982) Localization of type IV collagen, laminin, heparan sulfate proteoglycan, and fibronectin to the basal lamina of basement membranes. J Cell Biol 95: 340-344.
72. Lee J, Rieu P, Arnaout M, Liddington R (1995) Crystal structure of the A domain from the alpha subunit of integrin CR3 (CD11b/CD18). Cell 80: 631-638.
73. Legate K, Fässler R (2009) Mechanisms that regulate adaptor binding to beta-integrin cytoplasmic tails. J Cell Sci 122: 187-285.
74. Legate K, Takahashi S, Bonakdar N, Fabry B, Boettiger D, Zent R et al (2011) Integrin adhesion and force coupling are independently regulated by localized PtdIns(4, 5)2 synthesis. EMBO J 30: 4539-4553.
75. Lerea K, Venjara A, Olson S, Kelly M (2007) Threonine phosphorylation of integrin beta3 in calyculin A-treated platelets is selectively sensitive to 5'-iodotubercidin. Biochim Biophys Acta 1773: 185-191.
76. Luo B-H, Carman C, Springer T (2007) Structural basis of integrin regulation and signaling. Annu Rev Immunol 25: 619-666.
77. Luxenburg C, Winograd-Katz S, Addadi L, Geiger B (2012) Involvement of actin polymerization in podosome dynamics. J Cell Sci 125: 1666-1672.
78. Ma Y-Q, Qin J, Wu C, Plow E (2008) Kindlin-2 (Mig-2): a co-activator of beta3 integrins. J Cell Biol 181: 439-446.
79. Martins M, Bairos V (2002) Glycocalyx of lung epithelial cells. Int Rev Cytol 216: 131-173.
80. Mattila P, Lappalainen P (2008) Filopodia: molecular architecture and cellular functions. Nat Rev Mol Cell Biol 9: 446-454.
81. Monkley S, Zhou X, Kinston S, Giblett S, Hemmings L, Priddle H et al (2000) Disruption of the talin gene arrests mouse development at the gastrulation stage. Dev Dyn 219: 560-574.
82. Moser M, Nieswandt B, Ussar S, Pozgajova M, Fässler R (2008) Kindlin-3 is essential for integrin activation and platelet aggregation. Nat Med 14: 325-330.
83. Munger J, Huang X, Kawakatsu H, Griffiths M, Dalton S, Wu J et al (1999) The integrin alpha v beta 6 binds and activates latent TGF beta 1: a mechanism for regulating pulmonary inflammation and fibrosis. Cell 96: 319-328.
84. Murphy D, Courtneidge S (2011) The 'ins' and 'outs' of podosomes and invadopodia: characteristics, formation and function. Nat Rev Mol Cell Biol 12: 413-426.
85. Naylor MJ, Li N, Cheung J, Lowe ET, Lambert E, Marlow R et al (2005) Ablation of beta1 integrin in mammary epithelium reveals a key role for integrin in glandular morphogenesis and differentiation. J Cell Biol 171: 717-728.
86. Nobes C, Hall A (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.
87. Ochoa G, Slepnev V, Neff L, Ringstad N, Takei K, Daniell L et al (2000) A functional link between dynamin and the actin cytoskeleton at podosomes. J Cell Biol 150: 377-389.
88. Otey C, Vasquez G, Burridge K, Erickson B (1993) Mapping of the alpha-actinin binding site within the beta 1 integrin cytoplasmic domain. J Biol Chem 268: 21193-21197.
89. Pankov R, Cukierman E, Katz B, Matsumoto K, Lin D, Lin S et al (2000) Integrin dynamics and matrix assembly: tensin-dependent translocation of alpha(5)beta(1) integrins promotes early fibronectin fibrillogenesis. J Cell Biol 148: 1075-1090.
90. Pasquet J-M, Noury M, Nurden A (2002) Evidence that the platelet integrin alphaIIb beta3 is regulated by the integrin-linked kinase, ILK, in a PI3-kinase dependent pathway. Thromb Haemost 88: 115-122.
91. Petrich B, Marchese P, Ruggeri Z, Spiess S, Weichert R, Ye F et al (2007) Talin is required for integrin-mediated platelet function in hemostasis and thrombosis. J Exp Med 204: 3103-3111.
92. Popova S, Lundgren-Akerlund E, Wiig H, Gullberg D (2007) Physiology and pathology of collagen receptors. Acta Physiol (Oxford) 190: 179-187.
93. Puklin-Faucher E, Vogel V (2009) Integrin activation dynamics between the RGD-binding site and the headpiece hinge. J Biol Chem 284: 36557-36568.
94. Qu H, Tu Y, Shi X, Larjava H, Saleem M, Shattil S et al (2011) Kindlin-2 regulates podocyte adhesion and fibronectin matrix deposition through interactions with phosphoinositides and integrins. J Cell Sci 124: 879-891.
95. Rantala JK, Pouwels J, Pellinen T, Veltel S, Laasola P, Mattila E et al (2011) SHARPIN is an endogenous inhibitor of beta1-integrin activation. Nat Cell Biol 13: 1315-1324.
96. Reddy K, Smith D, Plow E (2008) Analysis of Fyn function in hemostasis and alphaIIbbeta3-integrin signaling. J Cell Sci 121: 1641-1648.
97. Rose D, Alon R, Ginsberg M (2007) Integrin modulation and signaling in leukocyte adhesion and migration. Immunol Rev 218: 126-134.
98. Rosenkranz A, Mayadas T (1999) Leukocyte-endothelial cell interactions-lessons from knockout mice. Exp Nephrol 7: 125-136.
99. Rottner K, Hall A, Small J (1999) Interplay between Rac and Rho in the control of substrate contact dynamics. Curr Biol 9: 640-648.
100. Sabri S, Soler M, Foa C, Pierres A, Benoliel A, Bongrand P (2000) Glycocalyx modulation is a physiological means of regulating cell adhesion. J Cell Sci 113(Pt 9): 1589-1600.
101. Sakai T, Li S, Docheva D, Grashoff C, Sakai K, Kostka G et al (2003) Integrin-linked kinase (ILK) is required for polarizing the epiblast, cell adhesion, and controlling actin accumulation. Genes Dev 17: 926-940.
102. Schaller M, Otey C, Hildebrand J, Parsons J (1995) Focal adhesion kinase and paxillin bind to peptides mimicking beta integrin cytoplasmic domains. J Cell Biol 130: 1181-1187.
103. Scharffetter-Kochanek K, Lu H, Norman K, van Nood N, Munoz F, Grabbe S et al (1998) Spontaneous skin ulceration and defective T cell function in CD18 null mice. J Exp Med 188: 119-131.
104. Schiller HB, Hermann MR, Polleux J, Vignaud T, Zanivan S, Friedel CC et al (2013) beta1- and alphav-class integrins cooperate to regulate myosin II during rigidity sensing of fibronectin-based microenvironments. Nat Cell Biol 15: 625-636.
105. Schürpf T, Springer T (2011) Regulation of integrin affinity on cell surfaces. EMBO J 30: 4712-4727.
106. Shattil S, Ginsberg M (1997) Integrin signaling in vascular biology. J Clin Invest 100: 5.
107. Shattil S, Newman P (2004) Integrins: dynamic scaffolds for adhesion and signaling in platelets. Blood 104: 1606-1615.
108. Sheppard D, Cohen D, Wang A, Busk M (1992) Transforming growth factor beta differentially regulates expression of integrin subunits in guinea pig airway epithelial cells. J Biol Chem 267: 17409-17414.
109. Shi M, Sundramurthy K, Liu B, Tan S-M, Law S, Lescar J (2005) The crystal structure of the plexin-semaphorin-integrin domain/hybrid domain/I-EGF1 segment from the human integrin beta2 subunit at 1. 8-A resolution. J Biol Chem 280: 30586-30593.
110. Shi X, Ma Y-Q, Tu Y, Chen K, Wu S, Fukuda K et al (2007) The MIG-2/integrin interaction strengthens cell-matrix adhesion and modulates cell motility. J Biol Chem 282: 20455-20466.
111. Shimaoka M, Takagi J, Springer T (2002) Conformational regulation of integrin structure and function. Annu Rev Biophys Biomol Struct 31: 485-516.
112. Shimaoka M, Xiao T, Liu J-H, Yang Y, Dong Y, Jun C-D et al (2003) Structures of the alpha L I domain and its complex with ICAM-1 reveal a shape-shifting pathway for integrin regulation. Cell 112: 99-111.
113. Takagi J, Erickson H, Springer T (2001) C-terminal opening mimics 'inside-out' activation of integrin alpha5beta1. Nat Struct Biol 8: 412-416.
114. Takagi J, Petre B, Walz T, Springer T (2002) Global conformational rearrangements in integrin extracellular domains in outside-in and inside-out signaling. Cell 110: 599-11.
115. van der Flier A, Sonnenberg A (2001) Function and interactions of integrins. Cell Tissue Res 305: 285-298.
116. Vinogradova O, Velyvis A, Velyviene A, Hu B, Haas T, Plow E et al (2002) A structural mechanism of integrin alpha(IIb)beta(3) "inside-out" activation as regulated by its cytoplasmic face. Cell 110: 587-597.
117. Vlahakis N, Young B, Atakilit A, Sheppard D (2005) The lymphangiogenic vascular endothelial growth factors VEGF-C and -D are ligands for the integrin alpha9beta1. J Biol Chem 280: 4544-4552.
118. Vlahakis N, Young B, Atakilit A, Hawkridge A, Issaka R, Boudreau N et al (2007) Integrin alpha9beta1 directly binds to vascular endothelial growth factor (VEGF)-A and contributes to VEGF-A-induced angiogenesis. J Biol Chem 282: 15187-15196.
119. Wegener K, Campbell I (2008) Transmembrane and cytoplasmic domains in integrin activation and protein-protein interactions (review). Mol Membr Biol 25: 376-387.
120. Wegener K, Partridge A, Han J, Pickford A, Liddington R, Ginsberg M et al (2007) Structural basis of integrin activation by talin. Cell 128: 171-182.
121. Wehrle-Haller B (2012) Assembly and disassembly of cell matrix adhesions. Curr Opin Cell Biol 24: 569-581.
122. Xia Y, Gil S, Carter W (1996) Anchorage mediated by integrin alpha6beta4 to laminin 5 (epiligrin) regulates tyrosine phosphorylation of a membrane-associated 80-kD protein. J Cell Biol 132: 727-740.
123. Xiao T, Takagi J, Coller B, Wang J-H, Springer T (2004) Structural basis for allostery in integrins and binding to fibrinogen-mimetic therapeutics. Nature 432: 59-67.
124. Xiong J, Stehle T, Diefenbach B, Zhang R, Dunker R, Scott D et al (2001) Crystal structure of the extracellular segment of integrin alpha Vbeta3. Science (New York) 294: 339-345.
125. Xiong J-P, Stehle T, Zhang R, Joachimiak A, Frech M, Goodman S et al (2002) Crystal structure of the extracellular segment of integrin alpha Vbeta3 in complex with an Arg-Gly-Asp ligand. Science (New York, NY) 296: 151-155.
126. Xiong J-P, Stehle T, Goodman S, Arnaout M (2003) New insights into the structural basis of integrin activation. Blood 102: 1155-1159.
127. Xiong J-P, Mahalingham B, Alonso J, Borrelli L, Rui X, Anand S et al (2009) Crystal structure of the complete integrin alphaVbeta3 ectodomain plus an alpha/beta transmembrane fragment. J Cell Biol 186: 589-600.
128. Zaidel-Bar R, Ballestrem C, Kam Z, Geiger B (2003) Early molecular events in the assembly of matrix adhesions at the leading edge of migrating cells. J Cell Sci 116: 4605-4613.
129. Zaidel-Bar R, Itzkovitz S, Ma'ayan A, Iyengar R, Geiger B (2007) Functional atlas of the integrin adhesome. Nat Cell Biol 9: 858-867.
130. Zamir E, Geiger B (2001) Molecular complexity and dynamics of cell-matrix adhesions. J Cell Sci 114: 3583-3590.
131. Zamir E, Katz B, Aota S, Yamada K, Geiger B, Kam Z (1999) Molecular diversity of cell-matrix adhesions. J Cell Sci 112(Pt 11): 1655-1669.
132. Zamir E, Katz M, Posen Y, Erez N, Yamada K, Katz B et al (2000) Dynamics and segregation of cell-matrix adhesions in cultured fibroblasts. Nat Cell Biol 2: 191-196.
133. Zhu J, Carman C, Kim M, Shimaoka M, Springer T, Luo B-H (2007) Requirement of alpha and beta subunit transmembrane helix separation for integrin outside-in signaling. Blood 110: 2475-2483.
134. Zhu J, Luo B-H, Xiao T, Zhang C, Nishida N, Springer T (2008) Structure of a complete integrin ectodomain in a physiologic resting state and activation and deactivation by applied forces. Mol Cell 32: 849-861.