Article | Published:

Juno is the egg Izumo receptor and is essential for mammalian fertilization

Nature volume 508, pages 483487 (24 April 2014) | Download Citation

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Abstract

Fertilization occurs when sperm and egg recognize each other and fuse to form a new, genetically distinct organism. The molecular basis of sperm–egg recognition is unknown, but is likely to require interactions between receptor proteins displayed on their surface. Izumo1 is an essential sperm cell-surface protein, but its receptor on the egg has not been described. Here we identify folate receptor 4 (Folr4) as the receptor for Izumo1 on the mouse egg, and propose to rename it Juno. We show that the Izumo1–Juno interaction is conserved within several mammalian species, including humans. Female mice lacking Juno are infertile and Juno-deficient eggs do not fuse with normal sperm. Rapid shedding of Juno from the oolemma after fertilization suggests a mechanism for the membrane block to polyspermy, ensuring eggs normally fuse with just a single sperm. Our discovery of an essential receptor pair at the nexus of conception provides opportunities for the rational development of new fertility treatments and contraceptives.

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Acknowledgements

This work was supported by the Wellcome Trust grant number 098051. Juno-deficient mice were generated by the Sanger Institute Mouse Genetics Project. We thank W. Skarnes and J. Bussell for advice on transgenic mice; J. Kerr for construct design; A. Bradley and L. Jovine for helpful comments on the manuscript; and M. Okabe and N. Inoue for the OBF13 antibody.

Author information

Affiliations

  1. Cell Surface Signalling Laboratory, Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK

    • Enrica Bianchi
    •  & Gavin J. Wright
  2. Mouse Production Team, Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK

    • Brendan Doe
  3. Electron and Advanced Light Microscopy Suite, Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK

    • David Goulding

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Contributions

E.B. and G.J.W. conceived the project, designed and analysed the experiments, and wrote the manuscript. E.B. performed all experiments with technical help from B.D. (ICSI) and D.G. (electron microscopy).

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Gavin J. Wright.

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https://doi.org/10.1038/nature13203

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