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Novel insights into the molecular mechanism of sperm–egg fusion via IZUMO1

  • JPR Symposium
  • Fusion in Fertilization: Interdisciplinary Collaboration among Plant and Animal Scientists
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Abstract

When a spermatozoon fertilizes an oocyte in mammals, there must be an extremely precise regulation system for successful gamete fusion to occur, which is the final step of fertilization. Using gene-modified animals, IZUMO1 on the sperm side and its receptor, JUNO, on the ovum side, have been unveiled as indispensable factors for triggering membrane fusion. We recently analyzed the detailed molecular machinery of the IZUMO1–JUNO recognition system and clarified the tertiary architecture of the IZUMO1–JUNO complex based on the crystal structure. Over the past 2 years, important discoveries have successively emerged, presenting a new perspective on fertilization. In this mini-review, I will initially explain the historical background of the molecular mechanism study of gamete fusion, and go on to describe our latest study data.

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References

  • Almeida EA, Huovila AP, Sutherland AE, Stephens LE, Calarco PG, Shaw LM, Mercurio AM, Sonnenberg A, Primakoff P, Myles DG, White JM (1995) Mouse egg integrin alpha 6 beta 1 functions as a sperm receptor. Cell 81:1095–1104

    Article  CAS  PubMed  Google Scholar 

  • Aydin H, Sultana A, Li S, Thavalingam A, Lee JE (2016) Molecular architecture of the human sperm IZUMO1 and egg JUNO fertilization complex. Nature 534:562–565

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bianchi E, Doe B, Goulding D, Wright GJ (2014) Juno is the egg Izumo receptor and is essential for mammalian fertilization. Nature 508:483–487

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Blobel CP, Wolfsberg TG, Turck CW, Myles DG, Primakoff P, White JM (1992) A potential fusion peptide and an integrin ligand domain in a protein active in sperm-egg fusion. Nature 356:248–252

    Article  CAS  PubMed  Google Scholar 

  • Cho C, Bunch DO, Faure JE, Goulding EH, Eddy EM, Primakoff P, Myles DG (1998) Fertilization defects in sperm from mice lacking fertilin beta. Science 281:1857–1859

    Article  CAS  PubMed  Google Scholar 

  • Ellerman DA, Pei J, Gupta S, Snell WJ, Myles D, Primakoff P (2009) Izumo is part of a multiprotein family whose members form large complexes on mammalian sperm. Mol Reprod Dev 76:1188–1199

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Han L, Nishimura K, Sadat Al Hosseini H, Bianchi E, Wright GJ, Jovine L (2016) Divergent evolution of vitamin B9 binding underlies Juno-mediated adhesion of mammalian gametes. Curr Biol 26:R100–R101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ikawa M, Inoue N, Benham AM, Okabe M (2010) Fertilization: a sperm’s journey to and interaction with the oocyte. J Clin Invest 120:984–994

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Inoue N, Ikawa M, Isotani A, Okabe M (2005) The immunoglobulin superfamily protein Izumo is required for sperm to fuse with eggs. Nature 434:234–238

    Article  CAS  PubMed  Google Scholar 

  • Inoue N, Ikawa M, Okabe M (2011) The mechanism of sperm-egg interaction and the involvement of IZUMO1 in fusion. Asian J Androl 13:81–87

    Article  CAS  PubMed  Google Scholar 

  • Inoue N, Hamada D, Kamikubo H, Hirata K, Kataoka M, Yamamoto M, Ikawa M, Okabe M, Hagihara Y (2013) Molecular dissection of IZUMO1, a sperm protein essential for sperm-egg fusion. Development 140:3221–3229

    Article  CAS  PubMed  Google Scholar 

  • Inoue N, Hagihara Y, Wright D, Suzuki T, Wada I (2015) Oocyte-triggered dimerization of sperm IZUMO1 promotes sperm-egg fusion in mice. Nat Commun 6:8858

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kaji K, Oda S, Shikano T, Ohnuki T, Uematsu Y, Sakagami J, Tada N, Miyazaki S, Kudo A (2000) The gamete fusion process is defective in eggs of Cd9-deficient mice. Nat Genet 24:279–282

    Article  CAS  PubMed  Google Scholar 

  • Kato K, Satouh Y, Nishimasu H, Kurabayashi A, Morita J, Fujihara Y, Oji A, Ishitani R, Ikawa M, Nureki O (2016) Structural and functional insights into IZUMO1 recognition by JUNO in mammalian fertilization. Nat Commun 7:12198

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim E, Yamashita M, Nakanishi T, Park KE, Kimura M, Kashiwabara S, Baba T (2006) Mouse sperm lacking ADAM1b/ADAM2 fertilin can fuse with the egg plasma membrane and effect fertilization. J Biol Chem 281:5634–5639

    Article  CAS  PubMed  Google Scholar 

  • Klinovska K, Sebkova N, Dvorakova-Hortova K (2014) Sperm-egg fusion: a molecular enigma of mammalian reproduction. Int J Mol Sci 15:10652–10668

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Le Naour F, Rubinstein E, Jasmin C, Prenant M, Boucheix C (2000) Severely reduced female fertility in CD9-deficient mice. Science 287:319–321

    Article  CAS  PubMed  Google Scholar 

  • Lorenzetti D, Poirier C, Zhao M, Overbeek PA, Harrison W, Bishop CE (2014) A transgenic insertion on mouse chromosome 17 inactivates a novel immunoglobulin superfamily gene potentially involved in sperm-egg fusion. Mamm Genome 25:141–148

    Article  CAS  PubMed  Google Scholar 

  • Miyado K, Yamada G, Yamada S, Hasuwa H, Nakamura Y, Ryu F, Suzuki K, Kosai K, Inoue K, Ogura A, Okabe M, Mekada E (2000) Requirement of CD9 on the egg plasma membrane for fertilization. Science 287:321–324

    Article  CAS  PubMed  Google Scholar 

  • Nishimura K, Han L, Bianchi E, Wright GJ, de Sanctis D, Jovine L (2016) The structure of sperm Izumo1 reveals unexpected similarities with Plasmodium invasion proteins. Curr Biol 26:R661–R662

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ohto U, Ishida H, Krayukhina E, Uchiyama S, Inoue N, Shimizu T (2016) Structure of IZUMO1–JUNO reveals sperm–oocyte recognition during mammalian fertilization. Nature 534:566–569

    Article  CAS  PubMed  Google Scholar 

  • Satouh Y, Inoue N, Ikawa M, Okabe M (2012) Visualization of the moment of mouse sperm-egg fusion and dynamic localization of IZUMO1. J Cell Sci 125:4985–4990

    Article  CAS  PubMed  Google Scholar 

  • Snell WJ, White JM (1996) The molecules of mammalian fertilization. Cell 85:629–637

    Article  CAS  PubMed  Google Scholar 

  • Zhu X, Bansal NP, Evans JP (2000) Identification of key functional amino acids of the mouse fertilin beta (ADAM2) disintegrin loop for cell–cell adhesion during fertilization. J Biol Chem 275:7677–7683

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by JSPS KAKENHI Grant Number JP26291052 and the Takeda Science Foundation.

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Correspondence to Naokazu Inoue.

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Inoue, N. Novel insights into the molecular mechanism of sperm–egg fusion via IZUMO1. J Plant Res 130, 475–478 (2017). https://doi.org/10.1007/s10265-016-0895-z

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  • DOI: https://doi.org/10.1007/s10265-016-0895-z

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