Oocyte-triggered dimerization of sperm IZUMO1 promotes sperm–egg fusion in mice

• Published in: Nature communications 2015-11, Vol.6 (1), p.8858-8858, Article 8858
• Main Authors: Inoue, Naokazu, Hagihara, Yoshihisa, Wright, Danelle, Suzuki, Takahisa, Wada, Ikuo
• Format: Article
• Language: English
• Subjects: 13/1; 14/19; 14/28; 14/35; 38/109; 38/22; 38/23; 42/41; 42/44; 631/136; 631/443/494; 631/80/79; 631/80/86; 64/60; 82/103; 82/83; Animals; Cell Adhesion; Cell Membrane - metabolism; Dimerization; Female; Fertilization; Fertilization in Vitro; Fluorescence Recovery After Photobleaching; Humanities and Social Sciences; Immunoglobulins - metabolism; Male; Membrane Proteins - metabolism; Mice; Microscopy, Electron, Scanning; multidisciplinary; Oocytes - metabolism; Optical Imaging; Receptors, Cell Surface - metabolism; Science; Science (multidisciplinary); Sperm-Ovum Interactions; Spermatozoa - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms9858

Sperm–egg fusion is indispensable for completing mammalian fertilization. Although the underlying molecular mechanisms are poorly understood, requirement of two spermatozoon factors, IZUMO1 and SPACA6, and two oocyte factors, CD9 and the IZUMO1 counter-receptor JUNO, has been proven by gene disruption, and the binding of cells to an oocyte can be reconstituted by ectopic expression of IZUMO1. Here we demonstrate that robust IZUMO1-dependent adhesion of sperm with an oocyte accompanies the dimerization of IZUMO1. Despite the intrinsic dimeric property of its N-terminal region, IZUMO1 is monomeric in spermatozoa. Interestingly, JUNO associates with monomeric IZUMO1, which is then quickly removed as tight adhesion of the two cells is subsequently established. We therefore propose that global structural rearrangement of IZUMO1 occurs on JUNO recognition and that this rearrangement may then initiate force generation to overcome repulsion between the juxtaposing membranes, through an unidentified receptor on the egg. Sperm-egg fusion is facilitated by the sperm-specific receptor IZUMO1 and the egg-specific counter-receptor JUNO. Here Inoue et al. show that JUNO first binds to monomeric IZUMO1; IZUMO1 then dimerizes and excludes JUNO from the sperm-egg interface, suggesting the existence of a IZUMO1 dimer receptor.