Skip to main content
SpringerLink
Log in

Structural and mechanical functions of integrins

  • Review
  • Published:
Biophysical Reviews Aims and scope Submit manuscript

Abstract

Integrins are ubiquitously expressed cell surface receptors that play a critical role in regulating the interaction between a cell and its microenvironment to control cell fate. These molecules are regulated either via their expression on the cell surface or through a unique bidirectional signalling mechanism. However, integrins are just the tip of the adhesome iceberg, initiating the assembly of a large range of adaptor and signalling proteins that mediate the structural and signalling functions of integrin. In this review, we summarise the structure of integrins and mechanisms by which integrin activation is controlled. The different adhesion structures formed by integrins are discussed, as well as the mechanical and structural roles integrins play during cell migration. As the function of integrin signalling can be quite varied based on cell type and context, an in depth understanding of these processes will aid our understanding of aberrant adhesion and migration, which is often associated with human pathologies such as cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Abram C, Lowell C (2009) The ins and outs of leukocyte integrin signaling. Annu Rev Immunol 27:339–362

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • Arnaout M, Mahalingam B, Xiong JP (2005) Integrin structure, allostery, and bidirectional signaling. Annu Rev Cell Dev Biol 21:381–791

    CAS  PubMed  Google Scholar 

  • Arnaout M, Goodman S, Xiong J-P (2007) Structure and mechanics of integrin-based cell adhesion. Curr Opin Cell Biol 19:495–507

    CAS  PubMed Central  PubMed  Google Scholar 

  • Atilgan E, Ovryn B (2009) Nucleation and growth of integrin adhesions. Biophys J 96:3555–3572

    CAS  PubMed Central  PubMed  Google Scholar 

  • Baker R, Koretzky G (2008) Regulation of T cell integrin function by adapter proteins. Immunol Res 42:132–176

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • Bell G (1978) Models for the specific adhesion of cells to cells. Science (New York, NY) 200:618–627

    CAS  Google Scholar 

  • Boettiger D (2012) Mechanical control of integrin-mediated adhesion and signaling. Curr Opin Cell Biol 24:592–599

    Google Scholar 

  • Boettiger D, Wehrle-Haller B (2010) Integrin and glycocalyx mediated contributions to cell adhesion identified by single cell force spectroscopy. J Phys 22:194101

    CAS  Google Scholar 

  • 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

    PubMed  Google Scholar 

  • 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

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bunch T (2010) Integrin alphaIIbbeta3 activation in Chinese hamster ovary cells and platelets increases clustering rather than affinity. J Biol Chem 285:1841–1849

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • Chao W-T, Kunz J (2009) Focal adhesion disassembly requires clathrin-dependent endocytosis of integrins. FEBS Lett 583:1337–1343

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed Central  PubMed  Google Scholar 

  • Chhabra E, Higgs H (2007) The many faces of actin: matching assembly factors with cellular structures. Nat Cell Biol 9:1110–1121

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cox S, Baur P, Haenelt B (1977) Retention of the glycocalyx after cell detachment by EGTA. J Histochem Cytochem 25:1368–1372

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • Fournier M, Sauser R, Ambrosi D, Meister J-J, Verkhovsky A (2010) Force transmission in migrating cells. J Cell Biol 188:287–297

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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

    CAS  PubMed Central  PubMed  Google Scholar 

  • Galbraith C, Yamada K, Galbraith J (2007) Polymerizing actin fibers position integrins primed to probe for adhesion sites. Science (New York) 315:992–995

    CAS  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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

    CAS  Google Scholar 

  • 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

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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

    CAS  PubMed Central  PubMed  Google Scholar 

  • Han D, Rodriguez L, Guan J (2001) Identification of a novel interaction between integrin beta1 and 14-3-3beta. Oncogene 20:346–357

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • Heino J (2007) The collagen family members as cell adhesion proteins. Bioessays 29:1001–1010

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • Humphries J, Byron A, Humphries M (2006) Integrin ligands at a glance. J Cell Sci 119:3901–3904

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hynes R (1992) Integrins: versatility, modulation, and signaling in cell adhesion. Cell 69:11–25

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • Ito S (1969) Structure and function of the glycocalyx. Fed Proc 28:12–25

    CAS  PubMed  Google Scholar 

  • Jaffe A, Hall A (2005) Rho GTPases: biochemistry and biology. Annu Rev Cell Dev Biol 21:247–269

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • Kim M, Carman C, Springer T (2003) Bidirectional transmembrane signaling by cytoplasmic domain separation in integrins. Science (New York) 301:1720–1725

    CAS  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • Legate K, Fässler R (2009) Mechanisms that regulate adaptor binding to beta-integrin cytoplasmic tails. J Cell Sci 122:187–285

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • Luo B-H, Carman C, Springer T (2007) Structural basis of integrin regulation and signaling. Annu Rev Immunol 25:619–666

    CAS  PubMed Central  PubMed  Google Scholar 

  • Luxenburg C, Winograd-Katz S, Addadi L, Geiger B (2012) Involvement of actin polymerization in podosome dynamics. J Cell Sci 125:1666–1672

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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

    CAS  PubMed Central  PubMed  Google Scholar 

  • Martins M, Bairos V (2002) Glycocalyx of lung epithelial cells. Int Rev Cytol 216:131–173

    CAS  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed Central  PubMed  Google Scholar 

  • Popova S, Lundgren-Akerlund E, Wiig H, Gullberg D (2007) Physiology and pathology of collagen receptors. Acta Physiol (Oxford) 190:179–187

    CAS  Google Scholar 

  • Puklin-Faucher E, Vogel V (2009) Integrin activation dynamics between the RGD-binding site and the headpiece hinge. J Biol Chem 284:36557–36568

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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

    CAS  PubMed Central  PubMed  Google Scholar 

  • Reddy K, Smith D, Plow E (2008) Analysis of Fyn function in hemostasis and alphaIIbbeta3-integrin signaling. J Cell Sci 121:1641–1648

    CAS  PubMed Central  PubMed  Google Scholar 

  • Rose D, Alon R, Ginsberg M (2007) Integrin modulation and signaling in leukocyte adhesion and migration. Immunol Rev 218:126–134

    CAS  PubMed  Google Scholar 

  • Rosenkranz A, Mayadas T (1999) Leukocyte-endothelial cell interactions—lessons from knockout mice. Exp Nephrol 7:125–136

    CAS  PubMed  Google Scholar 

  • Rottner K, Hall A, Small J (1999) Interplay between Rac and Rho in the control of substrate contact dynamics. Curr Biol 9:640–648

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • Schürpf T, Springer T (2011) Regulation of integrin affinity on cell surfaces. EMBO J 30:4712–4727

    PubMed Central  PubMed  Google Scholar 

  • Shattil S, Ginsberg M (1997) Integrin signaling in vascular biology. J Clin Invest 100:5

    Google Scholar 

  • Shattil S, Newman P (2004) Integrins: dynamic scaffolds for adhesion and signaling in platelets. Blood 104:1606–1615

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • Shimaoka M, Takagi J, Springer T (2002) Conformational regulation of integrin structure and function. Annu Rev Biophys Biomol Struct 31:485–516

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • Takagi J, Erickson H, Springer T (2001) C-terminal opening mimics ‘inside–out’ activation of integrin alpha5beta1. Nat Struct Biol 8:412–416

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • van der Flier A, Sonnenberg A (2001) Function and interactions of integrins. Cell Tissue Res 305:285–298

    PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • Wegener K, Campbell I (2008) Transmembrane and cytoplasmic domains in integrin activation and protein-protein interactions (review). Mol Membr Biol 25:376–387

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • Wehrle-Haller B (2012) Assembly and disassembly of cell matrix adhesions. Curr Opin Cell Biol 24:569–581

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • 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

    CAS  Google Scholar 

  • 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

    CAS  Google Scholar 

  • Xiong J-P, Stehle T, Goodman S, Arnaout M (2003) New insights into the structural basis of integrin activation. Blood 102:1155–1159

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zamir E, Geiger B (2001) Molecular complexity and dynamics of cell-matrix adhesions. J Cell Sci 114:3583–3590

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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

    CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgements

Financial support was provided by the Cancer Council NSW, Cancer Institute NSW, National Breast Cancer Foundation of Australia, National Health & Medical Research Council of Australia and the Prostate Cancer Foundation of Australia.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Discipline of Physiology & Bosch Institute, School of Medical Sciences, The University of Sydney, Sydney, NSW, Australia

    Luke R. Anderson, Thomas W. Owens & Matthew J. Naylor

  2. The University of Sydney, Room E212, Anderson Stuart Building (F13), Sydney, NSW, 2006, Australia

    Matthew J. Naylor

Authors
  1. Luke R. Anderson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thomas W. Owens
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Matthew J. Naylor
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Matthew J. Naylor.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Anderson, L.R., Owens, T.W. & Naylor, M.J. Structural and mechanical functions of integrins. Biophys Rev 6, 203–213 (2014). https://doi.org/10.1007/s12551-013-0124-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12551-013-0124-0

Keywords

Search

Navigation