Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi


  • Shoshana LevyEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_599


Historical Background

CD81 was originally identified as a Target of an Anti-Proliferative Antibody (TAPA-1) in a study that also defined a new family of transmembrane proteins, later named tetraspanins (Oren et al. 1990). CD81 is expressed on most human cell types; however, Oren et al. have shown that the sensitivity of diverse cell lineages to the anti-proliferative effect of the anti-CD81 antibody differed (Oren et al. 1990). Therefore, subsequent immune-co-precipitation studies were performed to reveal that CD81 associates with different partner proteins in the various cells types. For example, in B cells CD81 associates with CD19, a B cell specific signaling molecule. Similar studies on additional family members confirmed that tetraspanins tend to associate in the membrane with each other and with additional partner proteins. These tetraspanin-enriched microdomains (TEMs) are dynamic membrane entities, which act as signaling platforms (reviewed in (Levy...

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


  1. Brazzoli M, Bianchi A, Filippini S, Weiner A, Zhu Q, Pizza M, Crotta S. CD81 is a central regulator of cellular events required for hepatitis C virus infection of human hepatocytes. J Virol. 2008;82:8316–29.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Coffey GP, Rajapaksa R, Liu R, Sharpe O, Kuo CC, Krauss SW, Sagi Y, Davis RE, Staudt LM, Sharman JP, Robinson WH, Levy S. Engagement of CD81 induces ezrin tyrosine phosphorylation and its cellular redistribution with filamentous actin. J Cell Sci. 2009;122:3137–44.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Crotta S, Ronconi V, Ulivieri C, Baldari CT, Valiante NM, Abrignani S, Wack A. Cytoskeleton rearrangement induced by tetraspanin engagement modulates the activation of T and NK cells. Eur J Immunol. 2006;36:919–29.PubMedCrossRefGoogle Scholar
  4. Dubuisson J, Helle F, Cocquerel L. Early steps of the hepatitis C virus life cycle. Cell Microbiol. 2008;10:821–7.PubMedCrossRefGoogle Scholar
  5. Feigelson SW, Grabovsky V, Shamri R, Levy S, Alon R. The CD81 tetraspanin facilitates instantaneous leukocyte VLA-4 adhesion strengthening to vascular cell adhesion molecule 1 (VCAM-1) under shear flow. J Biol Chem. 2003;278:51203–12.PubMedCrossRefGoogle Scholar
  6. Garcia-Espana A, Chung PJ, Sarkar IN, Stiner E, Sun TT, Desalle R. Appearance of new tetraspanin genes during vertebrate evolution. Genomics. 2008;91:326–34.PubMedCrossRefGoogle Scholar
  7. Grigorov B, Attuil-Audenis V, Perugi F, Nedelec M, Watson S, Pique C, Darlix JL, Conjeaud H, Muriaux D. A role for CD81 on the late steps of HIV-1 replication in a chronically infected T cell line. Retrovirology. 2009;6:28.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Imai T, Kakizaki M, Nishimura M, Yoshie O. Molecular analyses of the association of CD4 with two members of the transmembrane 4 superfamily, CD81 and CD82. J Immunol. 1995;155:1229–39.PubMedPubMedCentralGoogle Scholar
  9. Kitadokoro K, Bordo D, Galli G, Petracca R, Falugi F, Abrignani S, Grandi G, Bolognesi M. CD81 extracellular domain 3D structure: insight into the tetraspanin superfamily structural motifs. EMBO J. 2001;20:12–8.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Levy S, Shoham T. The tetraspanin web modulates immune-signaling complexes. Nat Rev Immunol. 2005;5:136–48.PubMedCrossRefGoogle Scholar
  11. Little KD, Hemler ME, Stipp CS. Dynamic regulation of a GPCR-tetraspanin-G protein complex on intact cells: central role of CD81 in facilitating GPR56-Galpha q/11 association. Mol Biol Cell. 2004;15:2375–87.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 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;10:4007–15.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Pileri P, Uematsu Y, Campagnoli S, Galli G, Falugi F, Petracca R, Weiner AJ, Houghton M, Rosa D, Grandi G, Abrignani S. Binding of hepatitis C virus to CD81. Science. 1998;282:938–41.PubMedCrossRefGoogle Scholar
  14. Rocha-Perugini V, Montpellier C, Delgrange D, Wychowski C, Helle F, Pillez A, Drobecq H, Le Naour F, Charrin S, Levy S, Rubinstein E, Dubuisson J, Cocquerel L. The CD81 partner EWI-2wint inhibits hepatitis C virus entry. PLoS One. 2008;3:e1866.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Rubinstein E, Ziyyat A, Prenant M, Wrobel E, Wolf JP, Levy S, Le Naour F, Boucheix C. Reduced fertility of female mice lacking CD81. Dev Biol. 2006;290:351–8.PubMedCrossRefGoogle Scholar
  16. Seigneuret M. Complete predicted three-dimensional structure of the facilitator transmembrane protein and hepatitis C virus receptor CD81: conserved and variable structural domains in the tetraspanin superfamily. Biophys J. 2006;90:212–27.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Silvie O, Rubinstein E, Franetich JF, Prenant M, Belnoue E, Renia L, Hannoun L, Eling W, Levy S, Boucheix C, Mazier D. Hepatocyte CD81 is required for Plasmodium falciparum and Plasmodium yoelii sporozoite infectivity. Nat Med. 2003;9:93–6.PubMedCrossRefGoogle Scholar
  18. van Zelm MC, Smet J, Adams B, Mascart F, Schandene L, Janssen F, Ferster A, Kuo CC, Levy S, van Dongen JJ, van der Burg M. CD81 gene defect in humans disrupts CD19 complex formation and leads to antibody deficiency. J Clin Invest. 2010;120:1265–74.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.School of Medicine – Division of Oncology Center for Clinical Sciences ResearchStanford UniversityStanfordUSA