Advertisement

Integrin Structure and Functional Relation with Ion Channels

  • Annarosa Arcangeli
  • Andrea Becchetti
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 674)

Abstract

Physical and functional link between cell adhesion molecules and ion channels provide a rapid connection between extracellular environment and cell physiology. Growing evidence does shows that frequent cross talk occurs between these classes of membrane proteins. These interactions are being addressed in ever increasing molecular detail. Recent advances have given X-ray resolved structure of the extracellular domains of integrin receptors. Such a level of resolution is still not available for the transmembrane and intracellular domains. Nonetheless, current molecular biological work is unraveling an intricate network connecting the cytoplasmic integrin domains with the cytoskeleton, ion channels and variety of cellular messengers. Overall, these studies show that integrins and ion channels both present bidirectional signaling features. Extracellular signals are usually transduced by integrins to trigger cellular responses that may involve ion fluxes, which can offer further relay. Intracellular processes and ion channel engagement can in turn affect integrin activation and expression and thus cell adhesion to the extracellular matrix. Moreover, ion channels themselves can communicate extracellular messages to both the cytoplasmic environment and integrin themselves. These interactions appear to often depend on formation of multiprotein membrane complexes that can recruit other elements, such as growth factor receptors and cytoplasmic signaling proteins. This chapter provides a general introduction to the field by giving a brief historical introduction and summarizing the main features of integrin structure and link to the cytoplasmic proteins. In addition, it outlines the main cellular processes in which channel-integrin interplay is known to exert clear physiological and pathological roles.

Keywords

Focal Adhesion Kinase Integrin Activation Curr Opin Cell Biol Integrin alphaVbeta3 Cytoplasmic Integrin Domain 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    McCaig CD, Rajnicek AM, Song B et al. Controlling cell behavior electrically: current views and future potential. Physiol Rev 2005; 85:943–978.CrossRefPubMedGoogle Scholar
  2. 2.
    Edelman GM. Cell adhesion molecules in the regulation of animal form and tissue pattern. Annu Rev Cell Biol 1986; 2:81–116.CrossRefPubMedGoogle Scholar
  3. 3.
    Hynes RO. Integrins: versatility, modulation and signaling in cell adhesion. Cell 1992; 69:11–25.CrossRefPubMedGoogle Scholar
  4. 4.
    Needham J. Order and life. Yale University Press, 1936.Google Scholar
  5. 5.
    Hynes RO. Integrins: Bidirectional, allosteric signalling machines. Cell 2002; 110:673–687.CrossRefPubMedGoogle Scholar
  6. 6.
    dePereda JM, Wiche G, Liddington RC. Crystal structure of a tandem pair of fibronectin type III domains from the cytoplasmic tail of integrin α6β4. EMBO J 1999; 18:4087–4095.CrossRefGoogle Scholar
  7. 7.
    Liddington RC, Ginsberg MH. Integrin activation takes shape. J Cell Biol 2002; 158:833–839.CrossRefPubMedGoogle Scholar
  8. 8.
    Miranti CK, Brugge JS. Sensing the environment. A historical perspective of integrin signal transduction. Nat Cell Biol 2002; 4:E83–E90.CrossRefPubMedGoogle Scholar
  9. 9.
    Schwartz MA. Integrin signaling revisited. Trends Cell Biol 2001; 11:466–470.CrossRefPubMedGoogle Scholar
  10. 10.
    Ginsberg MH, Partridge A, Shattil SJ. Integrin regulation. Curr Opin Cell Biol 2005; 17:509–516.CrossRefPubMedGoogle Scholar
  11. 11.
    Arcangeli A, Becchetti A, Del Bene MR et al. Fibronectin-integrin binding promotes hyperpolarization of murine erythroleukemia cells. Biochem Biophys Res Commun 1991; 177:1266–1272.CrossRefPubMedGoogle Scholar
  12. 12.
    Becchetti A, Arcangeli A, Del Bene MR et al. Response to fibronectin-integrin interaction in leukaemia cells: delayed enhancing of a K+ current. Proc Roy Soc Lond B 1992; 248:235–240.CrossRefGoogle Scholar
  13. 13.
    Arcangeli A, Becchetti A, Mannini A et al. Integrin-mediated neurite outgrowth in neuroblastoma cells depends on the activation of potassium channels. J Cell Biol 1993; 122:1131–1143.CrossRefPubMedGoogle Scholar
  14. 14.
    Ingber DE, Prusty D, Frangioni JV et al. Control of intracellular pH and growth by fibronectin in capillary endothelial cells. J Cell Biol 1990; 110:1803–1811.CrossRefPubMedGoogle Scholar
  15. 15.
    Jaconi MEE, Theler JM, Schlegel W et al. Multiple elevations of cytosolic free Ca2 in human neutrophils: initiation by adherence receptors of the integrin family. J Cell Biol 1991; 112:1249–1257.CrossRefPubMedGoogle Scholar
  16. 16.
    Doherty P, Ashton SV, Moore SE et al. Morphoregulatory activities of NCAM and N-cadherin can be accounted for by G-protein dependent activation of L-and N-type neuronal calcium channels. Cell 1991; 67:21–33.CrossRefPubMedGoogle Scholar
  17. 17.
    Michishita M, Videm V, Arnaout MA. A novel divalent cation-binding site in the A domain of the beta 2 integrin CR3 (CD11b/CD18) is essential for ligand binding. Cell 1993; 72:857–867.CrossRefPubMedGoogle Scholar
  18. 18.
    Arnaout MA, Goodman SL, Xiong JP. Structure and mechanics of integrin-based cell adhesion. Curr Opin Cell Biol 2007; 19:495–507.CrossRefPubMedGoogle Scholar
  19. 19.
    Arnaout MA, Mahalingam B, Xiong JP. Integrin structure, allostery and bidirectional signaling. Annu Rev Cell Dev Biol 2005; 21:381–410.CrossRefPubMedGoogle Scholar
  20. 20.
    Xiong JP, Stehle T, Diefenbach B et al. Crystal structure of the extracellular segment of integrin alphaVbeta3. Science 2001; 294:339–345.CrossRefPubMedGoogle Scholar
  21. 21.
    Xiong JP, Stehle T, Zhang R et al. Crystal structure of the extracellular segment of integrin alphaVbeta3 in complex with an Arg-Gly-Asp ligand. Science 2002; 296:151–155.CrossRefPubMedGoogle Scholar
  22. 22.
    Xiong JP, Stehle T, Goodman SL et al. A novel adaptation of the integrin PSI domain revealed from its crystal structure. J Biol Chem 2004; 279:40252–40254.CrossRefPubMedGoogle Scholar
  23. 23.
    Nishida N, Xie C, Shimaoka M et al. Activation of leukocyte beta(2) integrins by conversion from bent to extended conformation. Immunity 2006; 25:583–594.CrossRefPubMedGoogle Scholar
  24. 24.
    Xiong JP, Stehle T, Goodman SL et al. New insights into the structural basis of integrin activation. Blood 2003; 102:1155–1159.CrossRefPubMedGoogle Scholar
  25. 25.
    Wegener KL, Campbell ID. Transmembrane and cytoplasmic domains in integrin activation and protein-protein interactions. Mol Membr Biol 2008; 25:376–387.CrossRefPubMedGoogle Scholar
  26. 26.
    Lau TL, Partridge AW, Ginsberg MH et al. Structure of the integrin β3 transmembrane segment in phospholipid bicelles and detergent micelles. Biochemistry 2008; 47:4008–4016.CrossRefPubMedGoogle Scholar
  27. 27.
    Lau T-L, Dua V, Ulmer TS. Structure of the integrin αIIb transmembrane segment. J Biol Chem 2008; 283:16162–16168.CrossRefPubMedGoogle Scholar
  28. 28.
    Luo BH, Springer TA, Takagi J. A specific interface between integrin transmembrane helices and affinity for ligand. PLoS Biol 2004; 2:776–786.Google Scholar
  29. 29.
    Kim M, Carman CV, Springer TA. Bidirectional transmembrane signaling by cytoplasmic domain separation in integrins. Science 2003; 301:1720–1725.CrossRefPubMedGoogle Scholar
  30. 30.
    Critchley DR, Gingras AR. Talin at a glance. J Cell Sci 2008; 121:1345–1347.CrossRefPubMedGoogle Scholar
  31. 31.
    Critchley DR. Focal adhesions—the cytoskeletal connections. Curr Opin Cell Biol 2000; 12:133–139.CrossRefPubMedGoogle Scholar
  32. 32.
    Dunker AK, Cortese MS, Romero P et al. Flexible nets. The roles of intrinsic disorder in protein interaction networks. FEBS J 2005; 272:5129–5148.CrossRefPubMedGoogle Scholar
  33. 33.
    Cherubini A, Hofmann G, Pillozzi S et al. Human ether-à-go-go-related gene 1 channels are physically linked to beta1 integrins and modulate adhesion-dependent signaling. Mol Biol Cell 2005; 16:2972–2983.CrossRefPubMedGoogle Scholar
  34. 34.
    Davis MJ. Regulation of ion channels by integrins. Cell Biochem Biophys 2002; 36:41–66.CrossRefPubMedGoogle Scholar
  35. 35.
    Arcangeli A, Becchetti A. Complex functional interaction between integrin receptors and ion channels. Trends Cell Biol 2006; 16:632–639.CrossRefGoogle Scholar
  36. 36.
    Browe DM, Baumgarten CM. Stretch of beta 1 integrin activates an outwardly rectifying chloride current via FAK and Src in rabbit ventricular myocytes. J Gen Physiol 2003; 122:689–702.CrossRefPubMedGoogle Scholar
  37. 37.
    Browe DM, Baumgarten CM. EGFR kinase regulates volume-sensitive chloride current elicited by integrin stretch via PI-3K and NADPH oxidase in ventricular myocytes. J Gen Physiol 2006; 127:237–251.CrossRefPubMedGoogle Scholar
  38. 38.
    Ren Z, Raucci FJ, Browe DM et al. Regulation of swelling-activated Cl currents by angiotensin II signalling and NADPH oxidase in rabbit ventricle. Cardiovasc Res 2008; 77:73–80.CrossRefPubMedGoogle Scholar
  39. 39.
    Levite M, Cahalon L, Peretz A et al. Extracellular K+ and opening of voltage-gated potassium channels activate T-cell integrin function: physical and functional association between Kv1.3 channels and beta1 integrins. J Exp Med 2001; 191:1167–1176.CrossRefGoogle Scholar
  40. 40.
    Ganor Y, Besser M, Ben-Zakay N et al. Human T-cells express a functional ionotropic glutamate receptor GluR3 and glutamate by itself triggers integrin-mediated adhesion to laminin and fibronectin and chemotactic migration. J Immunol 2003; 170:4362–4372.PubMedGoogle Scholar
  41. 41.
    Hofmann G, Bernabei PA, Crociani O et al. hERG K+ channels activation during β1 integrin-mediated adhesion to fibronectin induces an up regulation of αvβ3 integrin in the preosteoclastic leukemia cell line FLG 29.1. J Biol Chem 2001; 276:4923–4931.CrossRefPubMedGoogle Scholar
  42. 42.
    Lin B, Arai AC, Lynch G et al. Integrins regulate NMDA receptor-mediated synaptic currents. J Neurophysiol 2003; 89:2874–2878.CrossRefPubMedGoogle Scholar
  43. 43.
    Bernard-Trifilo JA, Kramar AE, Torp R et al. Integrin signaling cascades are operational in adult hippocampal synapses and modulate NMDA receptor physiology. J Neurochem 2005; 93:834–849.CrossRefPubMedGoogle Scholar
  44. 44.
    Lin C-Y, Lynch G, Gall, CM. AMPA receptor stimulation increases alpha5beta1 integrin surface expression, adhesive function and signaling. J Neurochem 2005; 94:531–546.CrossRefPubMedGoogle Scholar
  45. 45.
    Pillozzi S, Brizzi MF, Bernabei PA et al. VEGFR-1 (FLT-1) β1 integrin and hERG K+ channel form a macromolecular signaling complex in acute myeloid leukemia: role in cell migration and clinical outcome. Blood 2007; 110:1238–1250.CrossRefPubMedGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2010

Authors and Affiliations

  1. 1.Department of Biotechnology and BiosciencesUniversity of Milano-BicoccaMilanItaly
  2. 2.Department of Experimental Pathology and OncologyUniversity of FlorenceFlorenceItaly

Personalised recommendations