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. 1999 Feb 15;338(Pt 1):61–70.

Transmembrane 4 superfamily protein CD151 (PETA-3) associates with beta 1 and alpha IIb beta 3 integrins in haemopoietic cell lines and modulates cell-cell adhesion.

S Fitter 1, P M Sincock 1, C N Jolliffe 1, L K Ashman 1
PMCID: PMC1220025  PMID: 9931299

Abstract

CD151 (PETA-3/SFA-1) is a member of the transmembrane 4 superfamily (TM4SF) of cell-surface proteins and is expressed abundantly both on the cell surface and in intracellular membranes by the haemopoietic cell lines M07e, HEL and K562. In the presence of mild detergent (CHAPS), CD151 co-immunoprecipitated with integrin alpha 4 beta 1, alpha 5 beta 1, alpha 6 beta 1 and alpha IIb beta 3. The association of CD151 with alpha 4 beta 1 and alpha 5 beta 1 seemed to be constitutive, as it was not modified by treatment of M07e cells with cytokines that regulate integrin function by 'inside-out' signalling. CD151 also associated with other tetraspans in an apparently cell-type-specific fashion, as defined by its co-precipitation with CD9, CD63 and CD81 from M07e cells, but not from K562 cells, which express similar levels of these proteins. F(ab')2 fragments of monoclonal antibodies (mAbs) against CD151 caused homotypic adhesion of HEL and K562 cells that was dependent on energy and cytoskeletal integrity and was augmented in the presence of RGDS peptides. The adhesion was not blocked by function-inhibiting mAbs against beta 1 or beta 3 integrins, suggesting that cell-cell adhesion was not mediated by the binding of integrin to a cell-associated ligand. Furthermore, mAb CD151 did not affect adhesion of the cells to fibronectin, laminin, collagen or fibrinogen, which are ligands for alpha 4 beta 1, alpha 5 beta 1, alpha 6 beta 1 and alpha IIb beta 3 integrins. Taken together, these results indicate that the ligation of CD151 does not induce the up-regulation of integrin avidity, but might act as a component of integrin signalling complexes.

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Selected References

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  1. Angelisová P., Hilgert I., Horejsí V. Association of four antigens of the tetraspans family (CD37, CD53, TAPA-1, and R2/C33) with MHC class II glycoproteins. Immunogenetics. 1994;39(4):249–256. doi: 10.1007/BF00188787. [DOI] [PubMed] [Google Scholar]
  2. Ashman L. K., Aylett G. W., Cambareri A. C., Cole S. R. Different epitopes of the CD31 antigen identified by monoclonal antibodies: cell type-specific patterns of expression. Tissue Antigens. 1991 Nov;38(5):199–207. doi: 10.1111/j.1399-0039.1991.tb01898.x. [DOI] [PubMed] [Google Scholar]
  3. Ashman L. K., Aylett G. W., Mehrabani P. A., Bendall L. J., Niutta S., Cambareri A. C., Cole S. R., Berndt M. C. The murine monoclonal antibody, 14A2.H1, identifies a novel platelet surface antigen. Br J Haematol. 1991 Oct;79(2):263–270. doi: 10.1111/j.1365-2141.1991.tb04531.x. [DOI] [PubMed] [Google Scholar]
  4. Behr S., Schriever F. Engaging CD19 or target of an antiproliferative antibody 1 on human B lymphocytes induces binding of B cells to the interfollicular stroma of human tonsils via integrin alpha 4/beta 1 and fibronectin. J Exp Med. 1995 Nov 1;182(5):1191–1199. doi: 10.1084/jem.182.5.1191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bell G. M., Seaman W. E., Niemi E. C., Imboden J. B. The OX-44 molecule couples to signaling pathways and is associated with CD2 on rat T lymphocytes and a natural killer cell line. J Exp Med. 1992 Feb 1;175(2):527–536. doi: 10.1084/jem.175.2.527. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Berditchevski F., Bazzoni G., Hemler M. E. Specific association of CD63 with the VLA-3 and VLA-6 integrins. J Biol Chem. 1995 Jul 28;270(30):17784–17790. doi: 10.1074/jbc.270.30.17784. [DOI] [PubMed] [Google Scholar]
  7. Berditchevski F., Tolias K. F., Wong K., Carpenter C. L., Hemler M. E. A novel link between integrins, transmembrane-4 superfamily proteins (CD63 and CD81), and phosphatidylinositol 4-kinase. J Biol Chem. 1997 Jan 31;272(5):2595–2598. doi: 10.1074/jbc.272.5.2595. [DOI] [PubMed] [Google Scholar]
  8. Berditchevski F., Zutter M. M., Hemler M. E. Characterization of novel complexes on the cell surface between integrins and proteins with 4 transmembrane domains (TM4 proteins). Mol Biol Cell. 1996 Feb;7(2):193–207. doi: 10.1091/mbc.7.2.193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cole S. R., Aylett G. W., Harvey N. L., Cambareri A. C., Ashman L. K. Increased expression of c-Kit or its ligand Steel Factor is not a common feature of adult acute myeloid leukaemia. Leukemia. 1996 Feb;10(2):288–296. [PubMed] [Google Scholar]
  10. Du X. P., Plow E. F., Frelinger A. L., 3rd, O'Toole T. E., Loftus J. C., Ginsberg M. H. Ligands "activate" integrin alpha IIb beta 3 (platelet GPIIb-IIIa). Cell. 1991 May 3;65(3):409–416. doi: 10.1016/0092-8674(91)90458-b. [DOI] [PubMed] [Google Scholar]
  11. Escola J. M., Kleijmeer M. J., Stoorvogel W., Griffith J. M., Yoshie O., Geuze H. J. Selective enrichment of tetraspan proteins on the internal vesicles of multivesicular endosomes and on exosomes secreted by human B-lymphocytes. J Biol Chem. 1998 Aug 7;273(32):20121–20127. doi: 10.1074/jbc.273.32.20121. [DOI] [PubMed] [Google Scholar]
  12. Faull R. J., Wang J., Leavesley D. I., Puzon W., Russ G. R., Vestweber D., Takada Y. A novel activating anti-beta1 integrin monoclonal antibody binds to the cysteine-rich repeats in the beta1 chain. J Biol Chem. 1996 Oct 11;271(41):25099–25106. doi: 10.1074/jbc.271.41.25099. [DOI] [PubMed] [Google Scholar]
  13. Fearon D. T., Carter R. H. The CD19/CR2/TAPA-1 complex of B lymphocytes: linking natural to acquired immunity. Annu Rev Immunol. 1995;13:127–149. doi: 10.1146/annurev.iy.13.040195.001015. [DOI] [PubMed] [Google Scholar]
  14. Fitter S., Tetaz T. J., Berndt M. C., Ashman L. K. Molecular cloning of cDNA encoding a novel platelet-endothelial cell tetra-span antigen, PETA-3. Blood. 1995 Aug 15;86(4):1348–1355. [PubMed] [Google Scholar]
  15. Forsyth K. D. Anti-CD9 antibodies augment neutrophil adherence to endothelium. Immunology. 1991 Feb;72(2):292–296. [PMC free article] [PubMed] [Google Scholar]
  16. Ginsberg M. H., Du X., Plow E. F. Inside-out integrin signalling. Curr Opin Cell Biol. 1992 Oct;4(5):766–771. doi: 10.1016/0955-0674(92)90099-x. [DOI] [PubMed] [Google Scholar]
  17. Hadjiargyrou M., Kaprielian Z., Kato N., Patterson P. H. Association of the tetraspan protein CD9 with integrins on the surface of S-16 Schwann cells. J Neurochem. 1996 Dec;67(6):2505–2513. doi: 10.1046/j.1471-4159.1996.67062505.x. [DOI] [PubMed] [Google Scholar]
  18. Hancock W. W., Zola H., Atkins R. C. Antigenic heterogeneity of human mononuclear phagocytes: immunohistologic analysis using monoclonal antibodies. Blood. 1983 Dec;62(6):1271–1279. [PubMed] [Google Scholar]
  19. Hasegawa H., Utsunomiya Y., Kishimoto K., Yanagisawa K., Fujita S. SFA-1, a novel cellular gene induced by human T-cell leukemia virus type 1, is a member of the transmembrane 4 superfamily. J Virol. 1996 May;70(5):3258–3263. doi: 10.1128/jvi.70.5.3258-3263.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Hemler M. E., Huang C., Schwarz L. The VLA protein family. Characterization of five distinct cell surface heterodimers each with a common 130,000 molecular weight beta subunit. J Biol Chem. 1987 Mar 5;262(7):3300–3309. [PubMed] [Google Scholar]
  21. Hemler M. E., Mannion B. A., Berditchevski F. Association of TM4SF proteins with integrins: relevance to cancer. Biochim Biophys Acta. 1996 Jun 7;1287(2-3):67–71. doi: 10.1016/0304-419x(96)00007-8. [DOI] [PubMed] [Google Scholar]
  22. Hynes R. O. Integrins: versatility, modulation, and signaling in cell adhesion. Cell. 1992 Apr 3;69(1):11–25. doi: 10.1016/0092-8674(92)90115-s. [DOI] [PubMed] [Google Scholar]
  23. Imai T., Yoshie O. C33 antigen and M38 antigen recognized by monoclonal antibodies inhibitory to syncytium formation by human T cell leukemia virus type 1 are both members of the transmembrane 4 superfamily and associate with each other and with CD4 or CD8 in T cells. J Immunol. 1993 Dec 1;151(11):6470–6481. [PubMed] [Google Scholar]
  24. Indig F. E., Diaz-Gonzalez F., Ginsberg M. H. Analysis of the tetraspanin CD9-integrin alphaIIbbeta3 (GPIIb-IIIa) complex in platelet membranes and transfected cells. Biochem J. 1997 Oct 1;327(Pt 1):291–298. doi: 10.1042/bj3270291. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Kovach N. L., Carlos T. M., Yee E., Harlan J. M. A monoclonal antibody to beta 1 integrin (CD29) stimulates VLA-dependent adherence of leukocytes to human umbilical vein endothelial cells and matrix components. J Cell Biol. 1992 Jan;116(2):499–509. doi: 10.1083/jcb.116.2.499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Lagaudrière-Gesbert C., Le Naour F., Lebel-Binay S., Billard M., Lemichez E., Boquet P., Boucheix C., Conjeaud H., Rubinstein E. Functional analysis of four tetraspans, CD9, CD53, CD81, and CD82, suggests a common role in costimulation, cell adhesion, and migration: only CD9 upregulates HB-EGF activity. Cell Immunol. 1997 Dec 15;182(2):105–112. doi: 10.1006/cimm.1997.1223. [DOI] [PubMed] [Google Scholar]
  27. Lazo P. A., Cuevas L., Gutierrez del Arroyo A., Orúe E. Ligation of CD53/OX44, a tetraspan antigen, induces homotypic adhesion mediated by specific cell-cell interactions. Cell Immunol. 1997 Jun 15;178(2):132–140. doi: 10.1006/cimm.1997.1139. [DOI] [PubMed] [Google Scholar]
  28. Lévesque J. P., Leavesley D. I., Niutta S., Vadas M., Simmons P. J. Cytokines increase human hemopoietic cell adhesiveness by activation of very late antigen (VLA)-4 and VLA-5 integrins. J Exp Med. 1995 May 1;181(5):1805–1815. doi: 10.1084/jem.181.5.1805. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Maecker H. T., Todd S. C., Levy S. The tetraspanin superfamily: molecular facilitators. FASEB J. 1997 May;11(6):428–442. [PubMed] [Google Scholar]
  30. Mannion B. A., Berditchevski F., Kraeft S. K., Chen L. B., Hemler M. E. Transmembrane-4 superfamily proteins CD81 (TAPA-1), CD82, CD63, and CD53 specifically associated with integrin alpha 4 beta 1 (CD49d/CD29). J Immunol. 1996 Sep 1;157(5):2039–2047. [PubMed] [Google Scholar]
  31. Masellis-Smith A., Jensen G. S., Seehafer J. G., Slupsky J. R., Shaw A. R. Anti-CD9 monoclonal antibodies induce homotypic adhesion of pre-B cell lines by a novel mechanism. J Immunol. 1990 Mar 1;144(5):1607–1613. [PubMed] [Google Scholar]
  32. Masellis-Smith A., Shaw A. R. CD9-regulated adhesion. Anti-CD9 monoclonal antibody induce pre-B cell adhesion to bone marrow fibroblasts through de novo recognition of fibronectin. J Immunol. 1994 Mar 15;152(6):2768–2777. [PubMed] [Google Scholar]
  33. Nakamura K., Iwamoto R., Mekada E. Membrane-anchored heparin-binding EGF-like growth factor (HB-EGF) and diphtheria toxin receptor-associated protein (DRAP27)/CD9 form a complex with integrin alpha 3 beta 1 at cell-cell contact sites. J Cell Biol. 1995 Jun;129(6):1691–1705. doi: 10.1083/jcb.129.6.1691. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Nishibori M., Cham B., McNicol A., Shalev A., Jain N., Gerrard J. M. The protein CD63 is in platelet dense granules, is deficient in a patient with Hermansky-Pudlak syndrome, and appears identical to granulophysin. J Clin Invest. 1993 Apr;91(4):1775–1782. doi: 10.1172/JCI116388. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Oren R., Takahashi S., Doss C., Levy R., Levy S. TAPA-1, the target of an antiproliferative antibody, defines a new family of transmembrane proteins. Mol Cell Biol. 1990 Aug;10(8):4007–4015. doi: 10.1128/mcb.10.8.4007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Roberts J. J., Rodgers S. E., Drury J., Ashman L. K., Lloyd J. V. Platelet activation induced by a murine monoclonal antibody directed against a novel tetra-span antigen. Br J Haematol. 1995 Apr;89(4):853–860. doi: 10.1111/j.1365-2141.1995.tb08424.x. [DOI] [PubMed] [Google Scholar]
  37. Rubinstein E., Le Naour F., Billard M., Prenant M., Boucheix C. CD9 antigen is an accessory subunit of the VLA integrin complexes. Eur J Immunol. 1994 Dec;24(12):3005–3013. doi: 10.1002/eji.1830241213. [DOI] [PubMed] [Google Scholar]
  38. Rubinstein E., Le Naour F., Lagaudrière-Gesbert C., Billard M., Conjeaud H., Boucheix C. CD9, CD63, CD81, and CD82 are components of a surface tetraspan network connected to HLA-DR and VLA integrins. Eur J Immunol. 1996 Nov;26(11):2657–2665. doi: 10.1002/eji.1830261117. [DOI] [PubMed] [Google Scholar]
  39. Rubinstein E., Poindessous-Jazat V., Le Naour F., Billard M., Boucheix C. CD9, but not other tetraspans, associates with the beta1 integrin precursor. Eur J Immunol. 1997 Aug;27(8):1919–1927. doi: 10.1002/eji.1830270815. [DOI] [PubMed] [Google Scholar]
  40. Sander B., Andersson J., Andersson U. Assessment of cytokines by immunofluorescence and the paraformaldehyde-saponin procedure. Immunol Rev. 1991 Feb;119:65–93. doi: 10.1111/j.1600-065x.1991.tb00578.x. [DOI] [PubMed] [Google Scholar]
  41. Seehafer J. G., Shaw A. R. Evidence that the signal-initiating membrane protein CD9 is associated with small GTP-binding proteins. Biochem Biophys Res Commun. 1991 Aug 30;179(1):401–406. doi: 10.1016/0006-291x(91)91384-o. [DOI] [PubMed] [Google Scholar]
  42. Shaw A. R., Domanska A., Mak A., Gilchrist A., Dobler K., Visser L., Poppema S., Fliegel L., Letarte M., Willett B. J. Ectopic expression of human and feline CD9 in a human B cell line confers beta 1 integrin-dependent motility on fibronectin and laminin substrates and enhanced tyrosine phosphorylation. J Biol Chem. 1995 Oct 13;270(41):24092–24099. doi: 10.1074/jbc.270.41.24092. [DOI] [PubMed] [Google Scholar]
  43. Sincock P. M., Mayrhofer G., Ashman L. K. Localization of the transmembrane 4 superfamily (TM4SF) member PETA-3 (CD151) in normal human tissues: comparison with CD9, CD63, and alpha5beta1 integrin. J Histochem Cytochem. 1997 Apr;45(4):515–525. doi: 10.1177/002215549704500404. [DOI] [PubMed] [Google Scholar]
  44. Slupsky J. R., Seehafer J. G., Tang S. C., Masellis-Smith A., Shaw A. R. Evidence that monoclonal antibodies against CD9 antigen induce specific association between CD9 and the platelet glycoprotein IIb-IIIa complex. J Biol Chem. 1989 Jul 25;264(21):12289–12293. [PubMed] [Google Scholar]
  45. Szöllósi J., Horejsí V., Bene L., Angelisová P., Damjanovich S. Supramolecular complexes of MHC class I, MHC class II, CD20, and tetraspan molecules (CD53, CD81, and CD82) at the surface of a B cell line JY. J Immunol. 1996 Oct 1;157(7):2939–2946. [PubMed] [Google Scholar]
  46. Takahashi S., Doss C., Levy S., Levy R. TAPA-1, the target of an antiproliferative antibody, is associated on the cell surface with the Leu-13 antigen. J Immunol. 1990 Oct 1;145(7):2207–2213. [PubMed] [Google Scholar]
  47. Todd S. C., Lipps S. G., Crisa L., Salomon D. R., Tsoukas C. D. CD81 expressed on human thymocytes mediates integrin activation and interleukin 2-dependent proliferation. J Exp Med. 1996 Nov 1;184(5):2055–2060. doi: 10.1084/jem.184.5.2055. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Tomiyama Y., Kunicki T. J., Zipf T. F., Ford S. B., Aster R. H. Response of human platelets to activating monoclonal antibodies: importance of Fc gamma RII (CD32) phenotype and level of expression. Blood. 1992 Nov 1;80(9):2261–2268. [PubMed] [Google Scholar]
  49. Worthington R. E., Carroll R. C., Boucheix C. Platelet activation by CD9 monoclonal antibodies is mediated by the Fc gamma II receptor. Br J Haematol. 1990 Feb;74(2):216–222. doi: 10.1111/j.1365-2141.1990.tb02568.x. [DOI] [PubMed] [Google Scholar]
  50. Wright M. D., Tomlinson M. G. The ins and outs of the transmembrane 4 superfamily. Immunol Today. 1994 Dec;15(12):588–594. doi: 10.1016/0167-5699(94)90222-4. [DOI] [PubMed] [Google Scholar]
  51. Yáez-Mó M., Alfranca A., Cabañas C., Marazuela M., Tejedor R., Ursa M. A., Ashman L. K., de Landázuri M. O., Sánchez-Madrid F. Regulation of endothelial cell motility by complexes of tetraspan molecules CD81/TAPA-1 and CD151/PETA-3 with alpha3 beta1 integrin localized at endothelial lateral junctions. J Cell Biol. 1998 May 4;141(3):791–804. doi: 10.1083/jcb.141.3.791. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Zannettino A. C., Rayner J. R., Ashman L. K., Gonda T. J., Simmons P. J. A powerful new technique for isolating genes encoding cell surface antigens using retroviral expression cloning. J Immunol. 1996 Jan 15;156(2):611–620. [PubMed] [Google Scholar]

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