Skip to main content

Critical role of exosomes in sperm–egg fusion and virus-induced cell–cell fusion

Reproductive Medicine and Biology volume 12, pages 117–126 (2013)Cite this article

Abstract

In mammals, two integral membrane proteins, sperm IZUMO1 and egg CD9, regulate sperm–egg fusion, and their roles are critical, but yet unclear. Recent studies, however, indicate interesting connections between the sperm–egg fusion and virus-induced cell–cell fusion. First, CD9-containing exosome-like vesicles, which are released from wild-type eggs, can induce the fusion between sperm and CD9-deficient egg, even though CD9-deficient eggs are highly refractory to the fusion with sperm. This finding provides strong evidence for the involvement of CD9-containing, fusion-facilitating vesicles in the sperm–egg fusion. Secondly, there are similarities between the generation of retroviruses in the host cells and the formation of small cellular vesicles, termed exosomes, in mammalian cells. The exosomes are involved in intercellular communication through transfer of proteins and ribonucleic acids (RNAs) including mRNAs and microRNAs. These collective studies provide an insight into the molecular mechanism of membrane fusion events.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

References

  1. Almeida EA, Huovila AP, Sutherland AE, Stephens LE, Calarco PG, Shaw LM, Mercurio AM, Sonnenberg A, Primakoff P, Myles DG, White JM. Mouse egg integrin alpha 6 beta 1 functions as a sperm receptor. Cell. 1995;81:1095–104.

    Article  CAS  PubMed  Google Scholar 

  2. Chen H, Sampson NS. Mediation of sperm–egg fusion: evidence that mouse egg alpha6beta1 integrin is the receptor for sperm fertilinbeta. Chem Biol. 1999;6:1–10.

    Article  PubMed  Google Scholar 

  3. Blobel CP, Wolfsberg TG, Turck CW, Myles DG, Primakoff P, White JM. A potential fusion peptide and an integrin ligand domain in a protein active in sperm–egg fusion. Nature. 1992;356:248–52.

    Article  CAS  PubMed  Google Scholar 

  4. Wolfsberg TG, Bazan JF, Blobel CP, Myles DG, Primakoff P, White JM. The precursor region of a protein active in sperm–egg fusion contains a metalloprotease and a disintegrin domain: structural, functional, and evolutionary implications. Proc Natl Acad Sci USA. 1993;90:10783–7.

    Article  CAS  PubMed  Google Scholar 

  5. Weskamp G, Blobel CP. A family of cellular proteins related to snake venom disintegrins. Proc Natl Acad Sci USA. 1994;91:2748–51.

    Article  CAS  PubMed  Google Scholar 

  6. Myles DG, Kimmel LH, Blobel CP, White JM, Primakoff P. Identification of a binding site in the disintegrin domain of fertilin required for sperm–egg fusion. Proc Natl Acad Sci USA. 1994;91:4195–8.

    Article  CAS  PubMed  Google Scholar 

  7. Evans JP, Schultz RM, Kopf GS. Characterization of the binding of recombinant mouse sperm fertilin alpha subunit to mouse eggs: evidence for function as a cell adhesion molecule in sperm–egg binding. Dev Biol. 1997;187:94–106.

    Article  CAS  PubMed  Google Scholar 

  8. Yuan R, Primakoff P, Myles DG. A role for the disintegrin domain of cyritestin, a sperm surface protein belonging to the ADAM family, in mouse sperm–egg plasma membrane adhesion and fusion. J Cell Biol. 1997;137:105–12.

    Article  CAS  PubMed  Google Scholar 

  9. Waters SI, White JM. Biochemical and molecular characterization of bovine fertilin alpha and beta (ADAM 1 and ADAM 2): a candidate sperm–egg binding/fusion complex. Biol Reprod. 1997;56:1245–54.

    Article  CAS  PubMed  Google Scholar 

  10. Elices MJ, Osborn L, Takada Y, Crouse C, Luhowskyj S, Hemler ME, Lobb RR. VCAM-1 on activated endothelium interacts with the leukocyte integrin VLA-4 at a site distinct from the VLA-4/fibronectin binding site. Cell. 1990;60:577–84.

    Article  CAS  PubMed  Google Scholar 

  11. Menko AS, Boettiger D. Occupation of the extracellular matrix receptor, integrin, is a control point for myogenic differentiation. Cell. 1987;51:51–7.

    Article  CAS  PubMed  Google Scholar 

  12. Rosen GD, Sanes JR, LaChance R, Cunningham JM, Roman J, Dean DC. Roles for the integrin VLA-4 and its counter receptor VCAM-1 in myogenesis. Cell. 1992;69:1107–19.

    Article  CAS  PubMed  Google Scholar 

  13. Gumbiner BM. Cell adhesion: the molecular basis of tissue architecture and morphogenesis. Cell. 1996;84:345–57.

    Article  CAS  PubMed  Google Scholar 

  14. Schwander M, Leu M, Stumm M, Dorchies OM, Ruegg UT, Schittny J, Muller U. Beta1 integrins regulate myoblast fusion and sarcomere assembly. Dev Cell. 2003;4:673–85.

    Article  CAS  PubMed  Google Scholar 

  15. Evans JP. Fertilin beta and other ADAMs as integrin ligands: insights into cell adhesion and fertilization. Bioessays. 2001;23:628–39.

    Article  CAS  PubMed  Google Scholar 

  16. Bronson RA, Fusi FM, Calzi F, Doldi N, Ferrari A. Evidence that a functional fertilin-like ADAM plays a role in human sperm–oolemmal interactions. Mol Hum Reprod. 1999;5:433–40.

    Article  CAS  PubMed  Google Scholar 

  17. Zhu X, Bansal NP, Evans JP. Identification of key functional amino acids of the mouse fertilin beta (ADAM2) disintegrin loop for cell–cell adhesion during fertilization. J Biol Chem. 2000;275:7677–83.

    Article  CAS  PubMed  Google Scholar 

  18. McLaughlin EA, Frayne J, Bloomerg G, Hall L. Do fertilin beta and cyritestin play a major role in mammalian sperm–oolemma interactions? A critical re-evaluation of the use of peptide mimics in identifying specific oocyte recognition proteins. Mol Hum Reprod. 2001;7:313–7.

    Article  CAS  PubMed  Google Scholar 

  19. Cho C, Ge H, Branciforte D, Primakoff P, Myles DG. Analysis of mouse fertilin in wild-type and fertilin beta(−/−) sperm: evidence for C-terminal modification, alpha/beta dimerization, and lack of essential role of fertilin alpha in sperm–egg fusion. Dev Biol. 2000;222:289–95.

    Article  CAS  PubMed  Google Scholar 

  20. Miller BJ, Georges-Labouesse E, Primakoff P, Myles DG. Normal fertilization occurs with eggs lacking the integrin alpha6beta1 and is CD9-dependent. J Cell Biol. 2000;149:1289–96.

    Article  CAS  PubMed  Google Scholar 

  21. He ZY, Brakebusch C, Fassler R, Kreidberg JA, Primakoff P, Myles DG. None of the integrins known to be present on the mouse egg or to be ADAM receptors are essential for sperm–egg binding and fusion. Dev Biol. 2003;254:226–37.

    Article  CAS  PubMed  Google Scholar 

  22. Vjugina U, Zhu X, Oh E, Bracero NJ, Evans JP. Reduction of mouse egg surface integrin alpha9 subunit (ITGA9) reduces the egg’s ability to support sperm–egg binding and fusion. Biol Reprod. 2009;80:833–41.

    Article  CAS  PubMed  Google Scholar 

  23. Okabe M, Cummins JM. Mechanisms of sperm–egg interactions emerging from gene-manipulated animals. Cell Mol Life Sci. 2007;64:1945–58.

    Article  CAS  PubMed  Google Scholar 

  24. Ikawa M, Inoue N, Benham AM, Okabe M. Fertilization: a sperm’s journey to and interaction with the oocyte. J Clin Invest. 2010;120:984–94.

    Article  CAS  PubMed  Google Scholar 

  25. Ikawa M, Wada I, Kominami K, Watanabe D, Toshimori K, Nishimune Y, Okabe M. The putative chaperone calmegin is required for sperm fertility. Nature. 1997;387:607–11.

    Article  CAS  PubMed  Google Scholar 

  26. Yamagata K, Nakanishi T, Ikawa M, Yamaguchi R, Moss SB, Okabe M. Sperm from the calmegin-deficient mouse have normal abilities for binding and fusion to the egg plasma membrane. Dev Biol. 2002;250:348–57.

    Article  CAS  PubMed  Google Scholar 

  27. Ikawa M, Tokuhiro K, Yamaguchi R, Benham AM, Tamura T, Wada I, Satouh Y, Inoue N, Okabe M. Calsperin is a testis-specific chaperone required for sperm fertility. J Biol Chem. 2011;286:5639–46.

    Article  CAS  PubMed  Google Scholar 

  28. Tokuhiro K, Ikawa M, Benham AM, Okabe M. Protein disulfide isomerase homolog PDILT is required for quality control of sperm membrane protein ADAM3 and male fertility [corrected]. Proc Natl Acad Sci USA. 2012;109:3850–5.

    Article  CAS  PubMed  Google Scholar 

  29. Marcello MR, Jia W, Leary JA, Moore KL, Evans JP. Lack of tyrosylprotein sulfotransferase-2 activity results in altered sperm–egg interactions and loss of ADAM3 and ADAM6 in epididymal sperm. J Biol Chem. 2011;286:13060–70.

    Article  CAS  PubMed  Google Scholar 

  30. Kondoh G, Tojo H, Nakatani Y, Komazawa N, Murata C, Yamagata K, Maeda Y, Kinoshita T, Okabe M, Taguchi R, Takeda J. Angiotensin-converting enzyme is a GPI-anchored protein releasing factor crucial for fertilization. Nat Med. 2005;11:160–6.

    Article  CAS  PubMed  Google Scholar 

  31. Cho C, Bunch DO, Faure JE, Goulding EH, Eddy EM, Primakoff P, Myles DG. Fertilization defects in sperm from mice lacking fertilin beta. Science. 1998;281:1857–9.

    Article  CAS  PubMed  Google Scholar 

  32. Kim E, Yamashita M, Nakanishi T, Park KE, Kimura M, Kashiwabara S, Baba T. Mouse sperm lacking ADAM1b/ADAM2 fertilin can fuse with the egg plasma membrane and effect fertilization. J Biol Chem. 2006;281:5634–9.

    Article  CAS  PubMed  Google Scholar 

  33. Nishimura H, Cho C, Branciforte DR, Myles DG, Primakoff P. Analysis of loss of adhesive function in sperm lacking cyritestin or fertilin beta. Dev Biol. 2001;233:204–13.

    Article  CAS  PubMed  Google Scholar 

  34. Inoue N, Kasahara T, Ikawa M, Okabe M. Identification and disruption of sperm-specific angiotensin converting enzyme-3 (ACE3) in mouse. PLoS ONE. 2010;5:e10301.

    Article  PubMed  Google Scholar 

  35. Saxena DK, Tanii I, Yoshinaga K, Toshimori K. Role of intra-acrosomal antigenic molecules acrin 1 (MN7) and acrin 2 (MC41) in penetration of the zona pellucida in fertilization in mice. J Reprod Fertil. 1999;117:17–25.

    Article  CAS  PubMed  Google Scholar 

  36. Crosnier C, Bustamante LY, Bartholdson SJ, Bei AK, Theron M, Uchikawa M, Mboup S, Ndir O, Kwiatkowski DP, Duraisingh MT, Rayner JC, Wright GJ. Basigin is a receptor essential for erythrocyte invasion by Plasmodium falciparum. Nature. 2011;480:534–7.

    CAS  PubMed  Google Scholar 

  37. Saxena DK, Toshimori K. Molecular modifications of MC31/CE9, a sperm surface molecule, during sperm capacitation and the acrosome reaction in the rat: is MC31/CE9 required for fertilization? Biol Reprod. 2004;70:993–1000.

    Article  CAS  PubMed  Google Scholar 

  38. Huelsken J, Vogel R, Erdmann B, Cotsarelis G, Birchmeier W. β-Catenin controls hair follicle morphogenesis and stem cell differentiation in the skin. Cell. 2001;105:533–45.

    Article  CAS  PubMed  Google Scholar 

  39. Nagafuchi A, Takeichi M, Tsukita S. The 102 kD cadherin-associated protein: similarity to vinculin and posttranscriptional regulation of expression. Cell. 1991;65:849–57.

    Article  CAS  PubMed  Google Scholar 

  40. Nagafuchi A, Takeichi M. Cell binding function of E-cadherin is regulated by the cytoplasmic domain. EMBO J. 1988;7:3679–84.

    CAS  PubMed  Google Scholar 

  41. De Vries WN, Evsikov AV, Haac BE, Fancher KS, Holbrook AE, Kemler R, Solter D, Knowles BB. Maternal beta-catenin and E-cadherin in mouse development. Development. 2004;131:4435–45.

    Article  PubMed  Google Scholar 

  42. Takezawa Y, Yoshida K, Miyado K, Sato M, Nakamura A, Kawano N, Sakakibara K, Kondo T, Harada Y, Ohnami N, Kanai S, Miyado M, et al. β-catenin is a molecular switch that regulates transition of cell–cell adhesion to fusion. Sci Rep. 2011;1:68.

    Article  PubMed  Google Scholar 

  43. Valenta T, Hausmann G, Basler K. The many faces and functions of beta-catenin. EMBO J. 2012;31:2714–36.

    Article  CAS  PubMed  Google Scholar 

  44. Marin-Briggiler CI, Lapyckyj L, Gonzalez Echeverria MF, Rawe VY, Alvarez Sedo C, Vazquez-Levin MH. Neural cadherin is expressed in human gametes and participates in sperm–oocyte interaction events. Int J Androl. 2010;33:e228–39.

    Article  CAS  PubMed  Google Scholar 

  45. Ohgimoto S, Tabata N, Suga S, Nishio M, Ohta H, Tsurudome M, Komada H, Kawano M, Watanabe N, Ito Y. Molecular characterization of fusion regulatory protein-1 (FRP-1) that induces multinucleated giant cell formation of monocytes and HIV gp160-mediated cell fusion. FRP-1 and 4F2/CD98 are identical molecules. J Immunol. 1995;155:3585–92.

    CAS  PubMed  Google Scholar 

  46. Takahashi Y, Bigler D, Ito Y, White JM. Sequence-specific interaction between the disintegrin domain of mouse ADAM 3 and murine eggs: role of beta1 integrin-associated proteins CD9, CD81, and CD98. Mol Biol Cell. 2001;12:809–20.

    Article  CAS  PubMed  Google Scholar 

  47. Da Ros VG, Maldera JA, Willis WD, Cohen DJ, Goulding EH, Gelman DM, Rubinstein M, Eddy EM, Cuasnicu PS. Impaired sperm fertilizing ability in mice lacking cysteine-rich secretory protein 1 (CRISP1). Dev Biol. 2008;320:12–8.

    Article  PubMed  Google Scholar 

  48. Busso D, Goldweic NM, Hayashi M, Kasahara M, Cuasnicu PS. Evidence for the involvement of testicular protein CRISP2 in mouse sperm–egg fusion. Biol Reprod. 2007;76:701–8.

    Article  CAS  PubMed  Google Scholar 

  49. Yamatoya K, Yoshida K, Ito C, Maekawa M, Yanagida M, Takamori K, Ogawa H, Araki Y, Miyado K, Toyama Y, Toshimori K. Equatorin: identification and characterization of the epitope of the MN9 antibody in the mouse. Biol Reprod. 2009;81:889–97.

    Article  CAS  PubMed  Google Scholar 

  50. Toshimori K, Saxena DK, Tanii I, Yoshinaga K. An MN9 antigenic molecule, equatorin, is required for successful sperm-oocyte fusion in mice. Biol Reprod. 1998;59:22–9.

    Article  CAS  PubMed  Google Scholar 

  51. Inoue N, Nishikawa T, Ikawa M, Okabe M. Tetraspanin-interacting protein IGSF8 is dispensable for mouse fertility. Fertil Steril. 2012;98:465–70.

    Article  CAS  PubMed  Google Scholar 

  52. Grayson P, Civetta A. Positive selection and the evolution of izumo genes in mammals. Int J Evol Biol. 2012;2012:958164.

    PubMed  Google Scholar 

  53. Fujihara Y, Murakami M, Inoue N, Satouh Y, Kaseda K, Ikawa M, Okabe M. Sperm equatorial segment protein 1, SPESP1, is required for fully fertile sperm in mouse. J Cell Sci. 2010;123:1531–6.

    Article  CAS  PubMed  Google Scholar 

  54. Nishimura H, Gupta S, Myles DG, Primakoff P. Characterization of mouse sperm TMEM190, a small transmembrane protein with the trefoil domain: evidence for co-localization with IZUMO1 and complex formation with other sperm proteins. Reproduction. 2011;141:437–51.

    Article  CAS  PubMed  Google Scholar 

  55. Spiridonov NA, Wong L, Zerfas PM, Starost MF, Pack SD, Paweletz CP, Johnson GR. Identification and characterization of SSTK, a serine/threonine protein kinase essential for male fertility. Mol Cell Biol. 2005;25:4250–61.

    Article  CAS  PubMed  Google Scholar 

  56. Sosnik J, Miranda PV, Spiridonov NA, Yoon SY, Fissore RA, Johnson GR, Visconti PE. Tssk6 is required for Izumo relocalization and gamete fusion in the mouse. J Cell Sci. 2009;122:2741–9.

    Article  CAS  PubMed  Google Scholar 

  57. Miyado K, Yamada G, Yamada S, Hasuwa H, Nakamura Y, Ryu F, Suzuki K, Kosai K, Inoue K, Ogura A, Okabe M, Mekada E. Requirement of CD9 on the egg plasma membrane for fertilization. Science. 2000;287:321–4.

    Article  CAS  PubMed  Google Scholar 

  58. Le Naour F, Rubinstein E, Jasmin C, Prenant M, Boucheix C. Severely reduced female fertility in CD9-deficient mice. Science. 2000;287:319–21.

    Article  PubMed  Google Scholar 

  59. Kaji K, Oda S, Shikano T, Ohnuki T, Uematsu Y, Sakagami J, Tada N, Miyazaki S, Kudo A. The gamete fusion process is defective in eggs of CD9-deficient mice. Nat Genet. 2000;24:279–82.

    Article  CAS  PubMed  Google Scholar 

  60. Inoue N, Ikawa M, Isotani A, Okabe M. The immunoglobulin superfamily protein Izumo is required for sperm to fuse with eggs. Nature. 2005;434:234–8.

    Article  CAS  PubMed  Google Scholar 

  61. Hemler ME. Targeting of tetraspanin proteins—potential benefits and strategies. Nat Rev Drug Discov. 2008;7:747–58.

    Article  CAS  PubMed  Google Scholar 

  62. Miyake M, Koyama M, Seno M, Ikeyama S. Identification of the motility-related protein (MRP-1), recognized by monoclonal antibody M31-15, which inhibits cell motility. J Exp Med. 1991;174:1347–54.

    Article  CAS  PubMed  Google Scholar 

  63. Akutsu H, Miura T, Machida M, Birumachi J, Hamada A, Yamada M, Sullivan S, Miyado K, Umezawa A. Maintenance of pluripotency and self-renewal ability of mouse embryonic stem cells in the absence of tetraspanin CD9. Differentiation. 2009;78:137–42.

    Article  CAS  PubMed  Google Scholar 

  64. Zhu GZ, Miller BJ, Boucheix C, Rubinstein E, Liu CC, Hynes RO, Myles DG, Primakoff P. Residues SFQ (173–175) in the large extracellular loop of CD9 are required for gamete fusion. Development. 2002;129:1995–2002.

    CAS  PubMed  Google Scholar 

  65. Kaji K, Oda S, Miyazaki S, Kudo A. Infertility of CD9-deficient mouse eggs is reversed by mouse CD9, human CD9, or mouse CD81; polyadenylated mRNA injection developed for molecular analysis of sperm–egg fusion. Dev Biol. 2002;247:327–34.

    Article  CAS  PubMed  Google Scholar 

  66. Moribe H, Yochem J, Yamada H, Tabuse Y, Fujimoto T, Mekada E. Tetraspanin protein (TSP-15) is required for epidermal integrity in Caenorhabditis elegans. J Cell Sci. 2004;117:5209–20.

    Article  CAS  PubMed  Google Scholar 

  67. Moribe H, Konakawa R, Koga D, Ushiki T, Nakamura K, Mekada E. Tetraspanin is required for generation of reactive oxygen species by the dual oxidase system in Caenorhabditis elegans. Plos Genet. 2012;8:e1002957.

    Article  CAS  PubMed  Google Scholar 

  68. Kopczynski CC, Davis GW, Goodman CS. A neural tetraspanin, encoded by late bloomer, that facilitates synapse formation. Science. 1996;271:1867–70.

    Article  CAS  PubMed  Google Scholar 

  69. Todres E, Nardi JB, Robertson HM. The tetraspanin superfamily in insects. Insect Mol Biol. 2000;9:581–90.

    Article  CAS  PubMed  Google Scholar 

  70. Hassuna N, Monk PN, Moseley GW, Partridge LJ. Strategies for targeting tetraspanin proteins: potential therapeutic applications in microbial infections. BioDrugs. 2009;23:341–59.

    Article  CAS  PubMed  Google Scholar 

  71. Shiino T. Phylodynamic analysis of a viral infection network. Front Microbiol. 2012;3:278.

    Article  PubMed  Google Scholar 

  72. Garcia E, Pion M, Pelchen-Matthews A, Collinson L, Arrighi JF, Blot G, Leuba F, Escola JM, Demaurex N, Marsh M, Piguet V. HIV-1 trafficking to the dendritic cell-T-cell infectious synapse uses a pathway of tetraspanin sorting to the immunological synapse. Traffic. 2005;6:488–501.

    Article  CAS  PubMed  Google Scholar 

  73. Wiley RD, Gummuluru S. Immature dendritic cell-derived exosomes can mediate HIV-1 trans infection. Proc Natl Acad Sci USA. 2006;103:738–43.

    Article  CAS  PubMed  Google Scholar 

  74. 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.

    Article  CAS  PubMed  Google Scholar 

  75. 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.

    Article  CAS  PubMed  Google Scholar 

  76. Tanigawa M, Miyamoto K, Kobayashi S, Sato M, Akutsu H, Okabe M, Mekada E, Sakakibara K, Miyado M, Umezawa A, Miyado K. Possible involvement of CD81 in acrosome reaction of sperm in mice. Mol Reprod Dev. 2008;75:150–5.

    Article  PubMed  Google Scholar 

  77. Ohnami N, Nakamura A, Miyado M, Sato M, Kawano N, Yoshida K, Harada Y, Takezawa Y, Kanai S, Ono C, Takahashi Y, Kimura K, et al. CD81 and CD9 work independently as extracellular components upon fusion of sperm and oocyte. Biol Open. 2012;1:640–7.

    Article  CAS  PubMed  Google Scholar 

  78. Huang S, Yuan S, Dong M, Su J, Yu C, Shen Y, Xie X, Yu Y, Yu X, Chen S, Zhang S, Pontarotti P, et al. The phylogenetic analysis of tetraspanins projects the evolution of cell–cell interactions from unicellular to multicellular organisms. Genomics. 2005;86:674–84.

    Article  CAS  PubMed  Google Scholar 

  79. Chiu WH, Chandler J, Cnops G, Van Lijsebettens M, Werr W. Mutations in the TORNADO2 gene affect cellular decisions in the peripheral zone of the shoot apical meristem of Arabidopsis thaliana. Plant Mol Biol. 2007;63:731–44.

    Article  CAS  PubMed  Google Scholar 

  80. Lambou K, Tharreau D, Kohler A, Sirven C, Marguerettaz M, Barbisan C, Sexton AC, Kellner EM, Martin F, Howlett BJ, Orbach MJ, Lebrun MH. Fungi have three tetraspanin families with distinct functions. BMC Genomics. 2008;9:63.

    Article  PubMed  Google Scholar 

  81. Clergeot PH, Gourgues M, Cots J, Laurans F, Latorse MP, Pepin R, Tharreau D, Notteghem JL, Lebrun MH. PLS1, a gene encoding a tetraspanin-like protein, is required for penetration of rice leaf by the fungal pathogen Magnaporthe grisea. Proc Natl Acad Sci USA. 2001;98:6963–8.

    Article  CAS  PubMed  Google Scholar 

  82. Veneault-Fourrey C, Parisot D, Gourgues M, Lauge R, Lebrun MH, Langin T. The tetraspanin gene ClPLS1 is essential for appressorium-mediated penetration of the fungal pathogen Colletotrichum lindemuthianum. Fungal Genet Biol. 2005;42:306–18.

    Article  CAS  PubMed  Google Scholar 

  83. Lambou K, Malagnac F, Barbisan C, Tharreau D, Lebrun MH, Silar P. The crucial role of the Pls1 tetraspanin during ascospore germination in Podospora anserina provides an example of the convergent evolution of morphogenetic processes in fungal plant pathogens and saprobes. Eukaryot Cell. 2008;7:1809–18.

    Article  CAS  PubMed  Google Scholar 

  84. Mi S, Lee X, Li X, Veldman GM, Finnerty H, Racie L, LaVallie E, Tang XY, Edouard P, Howes S, Keith JC Jr, McCoy JM. Syncytin is a captive retroviral envelope protein involved in human placental morphogenesis. Nature. 2000;403:785–9.

    Article  CAS  PubMed  Google Scholar 

  85. Hernandez LD, Hoffman LR, Wolfsberg TG, White JM. Virus-cell and cell–cell fusion. Annu Rev Cell Dev Biol. 1996;12:627–61.

    Article  CAS  PubMed  Google Scholar 

  86. Couzin J. Cell biology: the ins and outs of exosomes. Science. 2005;308:1862–3.

    Article  CAS  PubMed  Google Scholar 

  87. Denzer K, Kleijmeer MJ, Heijnen HF, Stoorvogel W, Geuze HJ. Exosome: from internal vesicle of the multivesicular body to intercellular signaling device. J Cell Sci. 2000;113(Pt 19):3365–74.

    CAS  PubMed  Google Scholar 

  88. Simons M, Raposo G. Exosomes–vesicular carriers for intercellular communication. Curr Opin Cell Biol. 2009;21:575–81.

    Article  CAS  PubMed  Google Scholar 

  89. Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, Lotvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 2007;9:654–9.

    Article  CAS  PubMed  Google Scholar 

  90. Barraud-Lange V, Naud-Barriant N, Bomsel M, Wolf JP, Ziyyat A. Transfer of oocyte membrane fragments to fertilizing spermatozoa. FASEB J. 2007;21:3446–9.

    Article  CAS  PubMed  Google Scholar 

  91. Runge KE, Evans JE, He ZY, Gupta S, McDonald KL, Stahlberg H, Primakoff P, Myles DG. Oocyte CD9 is enriched on the microvillar membrane and required for normal microvillar shape and distribution. Dev Biol. 2007;304:317–25.

    Article  CAS  PubMed  Google Scholar 

  92. Miyado K, Yoshida K, Yamagata K, Sakakibara K, Okabe M, Wang X, Miyamoto K, Akutsu H, Kondo T, Takahashi Y, Ban T, Ito C, et al. The fusing ability of sperm is bestowed by CD9-containing vesicles released from eggs in mice. Proc Natl Acad Sci USA. 2008;105:12921–6.

    Article  CAS  PubMed  Google Scholar 

  93. Talbot P, DiCarlantonio G. Ultrastructure of opossum oocyte investing coats and their sensitivity to trypsin and hyaluronidase. Dev Biol. 1984;103:159–67.

    Article  CAS  PubMed  Google Scholar 

  94. Dandekar P, Aggeler J, Talbot P. Structure, distribution and composition of the extracellular matrix of human oocytes and cumulus masses. Hum Reprod. 1992;7:391–8.

    CAS  PubMed  Google Scholar 

  95. Saunders CM, Larman MG, Parrington J, Cox LJ, Royse J, Blayney LM, Swann K, Lai FA. PLC zeta: a sperm-specific trigger of Ca(2+) oscillations in eggs and embryo development. Development. 2002;129:3533–44.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This review is based on our previous studies, which were supported by a grant from The Ministry of Health, Labor and Welfare, and a grant-in-aid for Scientific Research, The Ministry of Education, Culture, Sports, and Technology of Japan.

Conflict of interest

The author declares that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Reproductive Biology, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya, Tokyo, 157-8535, Japan

    Yuichirou Harada, Keiichi Yoshida, Natsuko Kawano & Kenji Miyado

Authors
  1. Yuichirou Harada
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Keiichi Yoshida
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Natsuko Kawano
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kenji Miyado
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kenji Miyado.

About this article

Cite this article

Harada, Y., Yoshida, K., Kawano, N. et al. Critical role of exosomes in sperm–egg fusion and virus-induced cell–cell fusion. Reprod Med Biol 12, 117–126 (2013). https://doi.org/10.1007/s12522-013-0152-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12522-013-0152-2

Keywords

  • CD9
  • Exosome
  • Fertilization
  • Membrane fusion
  • Tetraspanin