Integrins

Overview

Journal Cell Tissue Res

Specialties Anatomy & Histology
Cell Biology

Date 2009 Aug 21

PMID 19693543

Citations 702

Authors

Malgorzata Barczyk

Sergio Carracedo

Donald Gullberg

Affiliations

Soon will be listed here.

Abstract

Integrins are cell adhesion receptors that are evolutionary old and that play important roles during developmental and pathological processes. The integrin family is composed of 24 alphabeta heterodimeric members that mediate the attachment of cells to the extracellular matrix (ECM) but that also take part in specialized cell-cell interactions. Only a subset of integrins (8 out of 24) recognizes the RGD sequence in the native ligands. In some ECM molecules, such as collagen and certain laminin isoforms, the RGD sequences are exposed upon denaturation or proteolytic cleavage, allowing cells to bind these ligands by using RGD-binding receptors. Proteolytic cleavage of ECM proteins might also generate fragments with novel biological activity such as endostatin, tumstatin, and endorepellin. Nine integrin chains contain an alphaI domain, including the collagen-binding integrins alpha1beta1, alpha2beta1, alpha10beta1, and alpha11beta1. The collagen-binding integrins recognize the triple-helical GFOGER sequence in the major collagens, but their ability to recognize these sequences in vivo is dependent on the fibrillar status and accessibility of the interactive domains in the fibrillar collagens. The current review summarizes some basic facts about the integrin family including a historical perspective, their structure, and their ligand-binding properties.

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References

Tanentzapf G, Devenport D, Godt D, Brown N . Integrin-dependent anchoring of a stem-cell niche. Nat Cell Biol. 2007; 9(12):1413-8. PMC: 3529653. DOI: 10.1038/ncb1660. View

Legate K, Fassler R . Mechanisms that regulate adaptor binding to beta-integrin cytoplasmic tails. J Cell Sci. 2009; 122(Pt 2):187-98. DOI: 10.1242/jcs.041624. View

Astrof N, Salas A, Shimaoka M, Chen J, Springer T . Importance of force linkage in mechanochemistry of adhesion receptors. Biochemistry. 2006; 45(50):15020-8. PMC: 1766327. DOI: 10.1021/bi061566o. View

Kiema T, Lad Y, Jiang P, Oxley C, Baldassarre M, Wegener K . The molecular basis of filamin binding to integrins and competition with talin. Mol Cell. 2006; 21(3):337-47. DOI: 10.1016/j.molcel.2006.01.011. View

Friedland J, Lee M, Boettiger D . Mechanically activated integrin switch controls alpha5beta1 function. Science. 2009; 323(5914):642-4. DOI: 10.1126/science.1168441. View

Gardner H, Kreidberg J, Koteliansky V, Jaenisch R . Deletion of integrin alpha 1 by homologous recombination permits normal murine development but gives rise to a specific deficit in cell adhesion. Dev Biol. 1996; 175(2):301-13. DOI: 10.1006/dbio.1996.0116. View

Forsberg E, Lindblom A, Paulsson M, Johansson S . Laminin isoforms promote attachment of hepatocytes via different integrins. Exp Cell Res. 1994; 215(1):33-9. DOI: 10.1006/excr.1994.1311. View

Nishida N, Xie C, Shimaoka M, Cheng Y, Walz T, Springer T . Activation of leukocyte beta2 integrins by conversion from bent to extended conformations. Immunity. 2006; 25(4):583-94. DOI: 10.1016/j.immuni.2006.07.016. View

Nishiuchi R, Murayama O, Fujiwara H, Gu J, Kawakami T, Aimoto S . Characterization of the ligand-binding specificities of integrin alpha3beta1 and alpha6beta1 using a panel of purified laminin isoforms containing distinct alpha chains. J Biochem. 2003; 134(4):497-504. DOI: 10.1093/jb/mvg185. View

10.

Oxvig C, Springer T . Experimental support for a beta-propeller domain in integrin alpha-subunits and a calcium binding site on its lower surface. Proc Natl Acad Sci U S A. 1998; 95(9):4870-5. PMC: 20180. DOI: 10.1073/pnas.95.9.4870. View

11.

Schulze B, Mann K, Poschl E, Yamada Y, Timpl R . Structural and functional analysis of the globular domain IVa of the laminin alpha 1 chain and its impact on an adjacent RGD site. Biochem J. 1996; 314 ( Pt 3):847-51. PMC: 1217134. DOI: 10.1042/bj3140847. View

12.

Caswell C, Barczyk M, Keene D, Lukomska E, Gullberg D, Lukomski S . Identification of the first prokaryotic collagen sequence motif that mediates binding to human collagen receptors, integrins alpha2beta1 and alpha11beta1. J Biol Chem. 2008; 283(52):36168-75. PMC: 2605992. DOI: 10.1074/jbc.M806865200. View

13.

Larjava H, Plow E, Wu C . Kindlins: essential regulators of integrin signalling and cell-matrix adhesion. EMBO Rep. 2008; 9(12):1203-8. PMC: 2603460. DOI: 10.1038/embor.2008.202. View

14.

Senetar M, Moncman C, McCann R . Talin2 is induced during striated muscle differentiation and is targeted to stable adhesion complexes in mature muscle. Cell Motil Cytoskeleton. 2006; 64(3):157-73. DOI: 10.1002/cm.20173. View

15.

Velling T, Collo G, Sorokin L, Durbeej M, Zhang H, Gullberg D . Distinct alpha 7A beta 1 and alpha 7B beta 1 integrin expression patterns during mouse development: alpha 7A is restricted to skeletal muscle but alpha 7B is expressed in striated muscle, vasculature, and nervous system. Dev Dyn. 1996; 207(4):355-71. DOI: 10.1002/(SICI)1097-0177(199612)207:4<355::AID-AJA1>3.0.CO;2-G. View

16.

Millward-Sadler S, Wright M, Lee H, Nishida K, Caldwell H, Nuki G . Integrin-regulated secretion of interleukin 4: A novel pathway of mechanotransduction in human articular chondrocytes. J Cell Biol. 1999; 145(1):183-9. PMC: 2148217. DOI: 10.1083/jcb.145.1.183. View

17.

Chen M, OConnor K . Integrin alpha6beta4 promotes expression of autotaxin/ENPP2 autocrine motility factor in breast carcinoma cells. Oncogene. 2005; 24(32):5125-30. DOI: 10.1038/sj.onc.1208729. View

18.

Stewart P, Nemerow G . Cell integrins: commonly used receptors for diverse viral pathogens. Trends Microbiol. 2007; 15(11):500-7. DOI: 10.1016/j.tim.2007.10.001. View

19.

Clements J, Newham P, Shepherd M, Gilbert R, Dudgeon T, Needham L . Identification of a key integrin-binding sequence in VCAM-1 homologous to the LDV active site in fibronectin. J Cell Sci. 1994; 107 ( Pt 8):2127-35. DOI: 10.1242/jcs.107.8.2127. View

20.

Santala P, Heino J . Regulation of integrin-type cell adhesion receptors by cytokines. J Biol Chem. 1991; 266(34):23505-9. View