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Rearrangement of integrins in avidity regulation by leukocytes

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Abstract

Leukocyte adhesion must be tightly controlled in order for leukocytes to patrol the body as nonadherent cells, yet stop and emigrate from the blood into tissues at sites of infection or inflammation. A key element in this process is activation of β2 integrins. While β2 integrin activation involves conformational changes that increase affinity for ligand, evidence is accumulating that rearrangement of integrins, resulting in increases in avidity, is at least as important in regulating binding capacity. Recent work has established the importance of diffusion and rearrangement of integrins to activation of leukocyte adhesion, and has begun to unravel the molecular basis of its regulation.

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References

  1. Dustin ML, Springer TA: T-cell receptor cross-linking transiently stimulates adhesiveness through LFA-1. Nature 1989;341:619–624

    Article  PubMed  CAS  Google Scholar 

  2. Lub M, van Kooyk Y, Figdor CG: Ins and outs of LFA-1. Immunol Today 1995;16(10):479–483.

    Article  PubMed  CAS  Google Scholar 

  3. Lollo BA, Chan KW, Hanson EM, Moy VT, Brian AA: Directevidence for two affinity states for lymphocyte function-associated antigen 1 on activated T cells [publishederratum appears in J Biol Chem 1994:1;269(13):10,184]. J Biol Chem 1993;268:21,693–21,700.

    CAS  Google Scholar 

  4. Lu C, Shimaoka M, Zang Q, Takagi J, Springer TA: Locking in alternate conformations of the integrin alpha L beta2 I domain with disulfide bonds reveals functional relationships among integrin domains. Proc Natl Acad Sci USA 1927; 98(5):2393–2398

    Article  Google Scholar 

  5. Shimaoka M, Lu C, Palframan RT, von Andrian UH, McCormack A, Takagi J, Springer TA: Reversibly locking a protein fold in an active conformation with a disulfide bond: integrin alphaL I domains with high affinity and antagonist activity in vivo. Proc Natl Acad Sci USA 1922;98(11): 6009–6014.

    Article  Google Scholar 

  6. Zhou X, Li J: Macrophage-enriched myristoylated alanine-rich C kinase substrate and its phosphorylation is required for the phorbol ester-stimulated diffusion of beta 2 integrin molecules. J Biol Chem 2000;275(26): 20,217–20,222.

    Article  CAS  Google Scholar 

  7. Zhou X, Li J, Kucik DF: The microtubule cytoskeleton participates in control of beta2 integrin avidity. J Biol Chem 2001;276(48): 44,762-44,769.

    Google Scholar 

  8. Jones SL, Wang J, Turck CW, Brown EJ: A role for the actin-bundling protein L-plastin in the regulation of leukocyte integrin function. Proc Natl Acad Sci USA 1998;95(16):9331–9336.

    Article  PubMed  CAS  Google Scholar 

  9. Kucik DF, Dustin ML, Miller JM, Brown EJ: Adhesion activating phorbol ester increases the mobility of leukocyte integrin LFA-1 in cultured lymphocytes. J Clin Invest 1996;97:2139–2144.

    Article  PubMed  CAS  Google Scholar 

  10. Kupfer A, Burn P, Singer SJ: The PMA-induced specific association of LFA-1 and talininintact cloned T helpercells. J Mol Cell Immunol 1990;4(6):317–325.

    PubMed  CAS  Google Scholar 

  11. Sheetz MP, Turney S, Qian H, Elson EL: Nanometre-level analysis demonstrates that lipid flow does not drive membrane glycoprotein movements. Nature 1989; 340:284–288 (see comments).

    Article  PubMed  CAS  Google Scholar 

  12. Kucik DF, Elson EL, Sheetz MP: Forward transport of glycoproteins on leading lamellipodia in locomoting cells. Nature 1989;340: 315–317 (see comments).

    Article  PubMed  CAS  Google Scholar 

  13. Kucik DF, Elson EL, Sheetz MP: Cell migration does not produce membrane flow. J Cell Biol 1990; 111:1617–1622.

    Article  PubMed  CAS  Google Scholar 

  14. Kucik DF, Kuo SC, Elson EL, Sheetz MP: Preferential attachment of membrane glycoproteins to the cytoskeleton at the leading edge of lamella. J Cell Biol 1991;114(5):1029–1036.

    Article  PubMed  CAS  Google Scholar 

  15. DeBrabander M, Nuydens R, Ishihara A, Holifield B, Jacobson K, Geerts H: Late raldiffusion and retrograde movements of individual cell surface components on single motile cells observed with nanovid microscopy. J Cell Biol 1991;112: 111–124.

    Article  CAS  Google Scholar 

  16. Qian H, Sheetz MP, Elson EL: Single particle tracking: analysis of diffusion and flow in two-dimensional systems. Biophys J 1991;60:910–921.

    Article  PubMed  CAS  Google Scholar 

  17. Corbi AL, Miller LJ, O'Connor K, Lee A, Larson RS, Springer TA: CDNA cloning and complete primary structure of the alpha subunit of a leukocyte adhesion glycoprotein P150,95. EMBO J 1987;6: 4023–4028.

    PubMed  CAS  Google Scholar 

  18. Jacobson K, Ishihara A, Inman R: Lateral diffusion of proteins in membranes. Annu Rev Physiol 1987;49:163–175.

    Article  PubMed  CAS  Google Scholar 

  19. Yauch RL, Felsenfeld DP, Kmeft SK, Chen LB, Sheetz MP, Hemler ME: Mutational evidence for control of cell adhesion through integrindiffusion clustering, independent of ligand binding. J Exp Med 1997;186(8):1347–1355.

    Article  PubMed  CAS  Google Scholar 

  20. Bell GI: Models for the specific adhesion of cells to cells. Science 1978;200:618–627.

    Article  PubMed  CAS  Google Scholar 

  21. Ward MD, Dembo M, Hammer DA: Kinetics of cell detachment: peeling of discrete receptor clusters. Biophys J 1994;67(6): 2522–2534

    PubMed  CAS  Google Scholar 

  22. van Kooyk Y, Weder P, Heije K, Figdor CG: Extracellular Ca2+ modulates leukocyte function-associated antigen-1 cell surface distribution on T lymphocytes and consequently affects cell adhesion. J Cell Biol 1994;124(6): 1061–1070.

    Article  PubMed  Google Scholar 

  23. Lub M, van Kooyk Y, van Vliet SJ, Figdor CG: Dual role of the actin cytoskeleton in regulating cell adhesion mediated by the integrin lymphocyte function-associated molecule-1. Mol Biol Cell 1997; 8(2):341–351.

    PubMed  CAS  Google Scholar 

  24. Stewart MP, McDowall A, Hogg N: LFA-1-mediated adhesion is regulated by cytoskeletal restraint and by a Ca2+-dependent protease, calpain. J Cell Biol 1998;140(3): 699–707.

    Article  PubMed  CAS  Google Scholar 

  25. Sampath R, Gallagher PJ, Pavalko FM. Cytoskeletal interactions with the leukocyte integrin beta2 vytoplasmic tail: activation-dependent regulation of associations with talin and alpha-actinin. J Biol Chem 1998;273(50):33,588–33,594.

    Article  CAS  Google Scholar 

  26. Valmu L, Fagerholm S, Suila H, Gahmberg CG: The cytoskeletal association of CD11/CD18 leukocyte integrins in phorbol ester-activated cells correlates with CD18 phosphorylation. Eur J Immunol 1999;29(7):2107–2118.

    Article  PubMed  CAS  Google Scholar 

  27. Liliental J, Chang DD: Rackl, a receptor for activated protein kinase C, interacts with integrin beta subunit. J Biol Chem 1998;273(4):2379–2383.

    Article  PubMed  CAS  Google Scholar 

  28. Tanaka Y, Minami Y, Mine S, et al: H-Ras signals to cytoskeletal machinery in induction of integrin-mediated adhesion of T cells. J Immuno 1999;163(11):6209–6216.

    CAS  Google Scholar 

  29. Laudanna C, Campbell JJ, Butcher EC: Role of Rho- in chemoattractant-activated leukocyte adhesion through integrins. Science 1996; 271(5251):981–983.

    Article  PubMed  CAS  Google Scholar 

  30. Bos JL: All in the family? New insights and questions regarding interconnectivity of Ras, Rapl and Ral. EMBO J 1998;17(23): 6776–6782.

    Article  PubMed  CAS  Google Scholar 

  31. Katagiri K, Hattori M, Minato N, Irie SK, Takatsu K, Kinashi T: Rap1 is a potent activation signal for leukocyte function-associated antigen 1 distinct from protein kinase C and phosphatidylinositol-3-OH kinase. Mol Cell Biol 2000; 20(6):1956–1969.

    Article  PubMed  CAS  Google Scholar 

  32. Reedquist KA, Ross E, Koop EA, et al: The small GTPase, Rap1, mediates CD31-induced integrin adhesion. J Cell Biol 2000;148(6): 1151–1158.

    Article  PubMed  CAS  Google Scholar 

  33. Moss J, Vaughan M: Molecules in the ARF orbit. J Biol Chem 1998; 273 (34):21,431–21,434.

    Article  CAS  Google Scholar 

  34. Frank SR, Hatfield JC, Casanova JE: Remodeling of the actin cytoskeleton is coordinately regulated by protein kinase C and the ADP-ribosylation factor nucleotide exchange factor ARNO. Mol Biol Cell 1998;9(11): 3133–3146.

    PubMed  CAS  Google Scholar 

  35. Nonnan JC, Jones D, Barry ST, Holt MR, Cockeroft S, Critchley DR: ARF1 mediates paxillin recruitment to focaladhesions and potentiates Rho-stimulated stress fiber formation in intact and permeabilized swiss 3T3 fibroblasts. J Cell Biol 1998;143(7): 1981–1995.

    Article  Google Scholar 

  36. Li J, Zhu Z, Bao Z: Role of MacMARCKS in integrin-dependent macrophage spreading and tyrosine phosphorylation of paxillin. J Biol Chem 1996;271(22): 12,985–12,990.

    CAS  Google Scholar 

  37. Geiger C, Nagel W, Boehm T, et al: Cytohesin-1 regulates beta-2 integrin-mediated adhesion through noth ARF-GEF function and interaction with LFA-1. EMBO J 2000; 19(11):2525–2536.

    Article  PubMed  CAS  Google Scholar 

  38. Yue L, Bao Z, Li J: Expression of MacMARCKS restores cell adhesion to ICAM-1-coated surface. Cell Adhesion Commun 2000; 7(5):359–366.

    Article  CAS  Google Scholar 

  39. Yue L, Bao Z, Li J: Phosphorylated form of MacMARCKS is essential to LFA-1-dependent cell-cell adhesion of U937 monocytic cells. J Cell Physiol 1999;181(2): 355–360.

    Article  PubMed  CAS  Google Scholar 

  40. Blystone SD, Williams MP, Slater SE, Brown EJ: Requirement of integrin beta3 tyrosine 747 for beta3 tyrosine phosphorylation and regulation of alphay beta3 avidity. J Biol Chem 1997;272(45): 28,757–28,761.

    Article  CAS  Google Scholar 

  41. Wang J, Chen H, Brown EJ: L-Plastin peptide activation of alpha(v) beta(3)-mediated adhesion requires integrin conformational change and actin filament disassembly. J Biol Chem 1927; 276(17):14,474–14,481.

    Google Scholar 

  42. Kucik DF, O'Toole TE, Zheleznyak A, Busettini DK, Brown EJ: Activation-enhanced alpha-(IIb) beta(3)-integrin-cytoskeleton interactions outside of focal contacts require the alpha-subunit. Mol Biol Cell 2001;12(5): 1509–1518.

    PubMed  CAS  Google Scholar 

  43. Kaverina I, Rottner K, Small JV: Targeting, capture, and stabilization of microtubules at early focal adhesions. J Cell Biol 1998;142(1): 181–190.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Research Service, Birmingham VA Medical Center, 35294, Birmingham, AL

    Dennis F. Kucik MD, PhD

  2. Department of Pathology, University of Alabama at Birmingham, 35294, Birmingham, AL

    Dennis F. Kucik MD, PhD

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  1. Dennis F. Kucik MD, PhD
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Correspondence to Dennis F. Kucik MD, PhD.

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Kucik, D.F. Rearrangement of integrins in avidity regulation by leukocytes. Immunol Res 26, 199–206 (2002). https://doi.org/10.1385/IR:26:1-3:199

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  • DOI: https://doi.org/10.1385/IR:26:1-3:199

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