Juno also known as folate receptor 4, folate receptor delta or IZUMO1R is a protein that in humans is encoded by the FOLR4 gene.[5] Juno is a member of the folate receptor family[6] and is GPI-anchored to the plasmalemma of the mammalian egg cell that recognizes its sperm-riding counterpart, IZUMO1, and facilitates fertilization. The protein was named after Juno, the Roman goddess of fertility and marriage.[7]

IZUMO1R
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesIZUMO1R, Folbp3, JUNO, FOLR4, Juno (protein), IZUMO1 receptor, JUNO, FR-delta
External IDsOMIM: 615737; MGI: 1929185; HomoloGene: 11283; GeneCards: IZUMO1R; OMA:IZUMO1R - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001080486
NM_001199206
NM_001393610

NM_022888
NM_176807

RefSeq (protein)

NP_001186135

NP_075026
NP_789777

Location (UCSC)Chr 11: 94.3 – 94.31 MbChr 9: 14.8 – 14.82 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

After the initial fertilisation stage, a sudden decrease of Juno from the egg cell surface occurs and Juno becomes virtually undetectable after just 40 minutes.[7][8] Still, after fertilization via intracytoplasmic sperm injection, the egg cell does not lose cell-surface expression of Juno, which suggests that Juno contributes to the prevention of polyspermy.[8] Mice lacking Juno on the surface of their egg cells are infertile because their egg cells do not fuse with normal sperm, demonstrating Juno's essential role in the fertility of female mice.[7]

Discovery

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Based on a sequence homology search for genes relate to the folate receptor, the gene for folate receptor 4 was first identified in mice and humans in 2000 at the University of Nebraska.[6]

In 2014, the function of folate receptor 4 was discovered by the researchers of the Wellcome Trust Sanger Institute who also proposed that the protein be renamed as Juno.[8] Juno was initially found in murine oocytes, but its interaction with Izumo was subsequently found in other mammalian species, including humans.[8][9][10][11] Being previously elusive, Juno was discovered nine years after its male counterpart, Izumo1.[7]

3D structure

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The crystal structure of Juno (PDB: 5EJN​) was reported in February 2016 by researchers at Karolinska Institutet, in collaboration with the group at the Wellcome Trust Sanger Institute.[12]

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000183560Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000031933Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ "Entrez Gene: Folate receptor 4, delta (putative)".
  6. ^ a b Spiegelstein O, Eudy JD, Finnell RH (Nov 2000). "Identification of two putative novel folate receptor genes in humans and mouse". Gene. 258 (1–2): 117–25. doi:10.1016/S0378-1119(00)00418-2. PMID 11111049.
  7. ^ a b c d "Sperm meets egg: protein essential for fertilization discovered". Wellcome Trust Sanger Institute. 16 April 2014. Retrieved 16 April 2014.
  8. ^ a b c d Mayer K (16 April 2014). "Sperm/Egg Fusion Depends on Pairing of His/Her Proteins". Genetic Engineering & Biotechnology News. Retrieved 16 April 2014.
  9. ^ Bianchi E, Doe B, Goulding D, Wright GJ (Apr 2014). "Juno is the egg Izumo receptor and is essential for mammalian fertilization". Nature. 508 (7497): 483–7. Bibcode:2014Natur.508..483B. doi:10.1038/nature13203. PMC 3998876. PMID 24739963.
  10. ^ Everts S (16 April 2014). "Sperm Protein Meets Its Match". Chemical & Engineering News. 92 (16).
  11. ^ Anthony Rivas (16 April 2014). "'Juno' Protein Connects Egg To Sperm; Scientists Finally Unravel Mystery Of How The Cells Bond". Medical Daily. Retrieved 16 April 2014.
  12. ^ 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 (3): R100-1. Bibcode:2016CBio...26.R100H. doi:10.1016/j.cub.2015.12.034. PMC 4751342. PMID 26859261. PDB: 5EJN