title: Juno is the egg Izumo receptor and is essential for mammalian fertilization.
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.
authors.affiliation: Cell Surface Signalling Laboratory, Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK.
authors.forename: Enrica
authors.initials: E
authors.lastname: Bianchi
authors.affiliation: Mouse Production Team, Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK.
authors.forename: Brendan
authors.initials: B
authors.lastname: Doe
authors.affiliation: Electron and Advanced Light Microscopy Suite, Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK.
authors.forename: David
authors.initials: D
authors.lastname: Goulding
authors.affiliation: Cell Surface Signalling Laboratory, Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK.
authors.forename: Gavin J
authors.initials: GJ
authors.lastname: Wright
mesh_terms: D000818:Animals; D017124:Conserved Sequence; D019143:Evolution, Molecular; D005260:Female; D005298:Fertility / Q000235:genetics; D005306:Fertilization / Q000235:genetics / Q000502:physiology*; D020043:Genes, Essential; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism*; D007247:Infertility, Female / Q000235:genetics; D008297:Male; D008322:Mammals; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D010063:Ovum / Q000166:cytology / Q000378:metabolism*; D010312:Parthenogenesis; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D020554:Sperm Injections, Intracytoplasmic; D013094:Spermatozoa / Q000378:metabolism*; D013997:Time Factors
chemical_list: D017261:Glycosylphosphatidylinositols; D007136:Immunoglobulins; C498177:Izumo1 protein, mouse; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; C543634:folate receptor 4, mouse
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