IZUMO1 explained

Izumo sperm-egg fusion protein 1 (Sperm-specific protein izumo) is encoded in humans by the IZUMO1 gene.^[1] In mammalian fertilisation, IZUMO1 binds to its egg receptor counterpart, Juno, to facilitate recognition and fusion of the gametes. ^[2]

Function

The sperm-specific protein Izumo, named for a Japanese shrine dedicated to marriage, is essential for sperm-egg plasma membrane binding and fusion.^[3]

Studies have shown that male Izumo knockout mice are sterile because their sperm are unable to fuse to the oocyte membrane.[1] Izumo -/- mice produced morphologically normal sperm that were able to penetrate the zona pellucida, but could not fuse with to the eggs. In fact, it is necessary to relocate the IZUMO1 to the site of oocyte fusion.^[4] In-vitro human experiments have also been conducted, suggesting that Izumo is required for human gamete fusion. [1]

Through the use of Western Blot analyses, it has been shown that Izumo is only expressed in the testis and is found on mature spermatozoa. ^[5] Izumo-1 located on mature spermatozoa that have undergone capacitation binds to its receptor Juno, which is located on the oolemma of eggs. ^[6]

Further reading

• Chu AY, Workalemahu T, Paynter NP, Rose LM, Giulianini F, Tanaka T, Ngwa JS, Qi Q, Curhan GC, Rimm EB, Hunter DJ, Pasquale LR, Ridker PM, Hu FB, Chasman DI, Qi L . Novel locus including FGF21 is associated with dietary macronutrient intake . . 22 . 9 . 1895–902 . 2013 . 23372041 . 10.1093/hmg/ddt032 . 3612009.
• Yatsenko AN, Roy A, Chen R, Ma L, Murthy LJ, Yan W, Lamb DJ, Matzuk MM . Non-invasive genetic diagnosis of male infertility using spermatozoal RNA: KLHL10 mutations in oligozoospermic patients impair homodimerization . Human Molecular Genetics. 15 . 23 . 3411–9 . 2006 . 17047026 . 10.1093/hmg/ddl417 . free .
• Granados-Gonzalez V, Aknin-Seifer I, Touraine RL, Chouteau J, Wolf JP, Levy R . Preliminary study on the role of the human IZUMO gene in oocyte-spermatozoa fusion failure . Fertility and Sterility. 90 . 4 . 1246–8 . 2008 . 18082733 . 10.1016/j.fertnstert.2007.09.008 . free .
• Ellerman DA, Pei J, Gupta S, Snell WJ, Myles D, Primakoff P . Izumo is part of a multiprotein family whose members form large complexes on mammalian sperm . Molecular Reproduction and Development. 76 . 12 . 1188–99 . 2009 . 19658160 . 3779078 . 10.1002/mrd.21092 .
• Grayson P, Civetta A . Positive Selection and the Evolution of izumo Genes in Mammals . International Journal of Evolutionary Biology. 2012 . 958164 . 2012 . 22957301 . 3432370 . 10.1155/2012/958164 . free .
• Inoue N, Ikawa M, Okabe M . Putative sperm fusion protein IZUMO and the role of N-glycosylation . Biochemical and Biophysical Research Communications. 377 . 3 . 910–4 . 2008 . 18952059 . 10.1016/j.bbrc.2008.10.073 .

Notes and References

1. Web site: Entrez Gene: Izumo sperm-egg fusion 1 .
2. Bianchi, Enrica, et al. "Juno is the egg Izumo receptor and is essential for mammalian fertilization." Nature 508.7497 (2014): 483.
3. Inoue N, Ikawa M, Isotani A, Okabe M . The immunoglobulin superfamily protein Izumo is required for sperm to fuse with eggs . Nature . 434 . 7030 . 234–8 . 2005 . 15759005 . 10.1038/nature03362 . 2005Natur.434..234I . 4402928 .
4. Ikawa, M., Inoue, N., Benham, A. M., & Okabe, M. (2010). Fertilization: a sperm's journey to and interaction with the oocyte. The Journal of clinical investigation, 120(4), 984-94.
5. Ellerman DA, Pei J, Gupta S, Snell WJ, Myles D, Primakoff P. Izumo is part of a multiprotein family whose members form large complexes on mammalian sperm. Molecular reproduction and development. 2009;76(12):1188-1199.
6. Bianchi E, Doe B, Goulding D, Sanger Mouse Genetics Project, Wright GJ. Juno is the egg Izumo receptor and is essential for mammalian fertilisation. Nature. 2014;508(7497):483-487.