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UniProt release 2014_06

Published June 11, 2014


Everything you always wanted to know about... sperm-egg interaction

To reach the ultimate goal of sexual reproduction which is egg fertilization, sperm cells have to run an obstacle course. They have to jump, or rather to swim, through a lot of hoops and hurdles before fusing with the oocyte and forming a zygote. The very first step of this race starts after ejaculation and involves sperm capacitation, a complex process characterized by a series of structural and functional changes, leading to sperm hypermotility that allows it to swim through oviductal mucus. In the ampulla of the fallopian tube, in the immediate surroundings of the oocyte, the spermatozoon meets a hyaluronic acid-rich matrix secreted by cumulus cells that it penetrates with the help of hyaluronidase PH-20/SPAM1. The next impediment is the egg’s coat, the zona pellucida. The interaction between the spermatozoon and zona pellucida leads to the acrosomal reaction, in which molecules required for penetrating the zona pellucida are secreted and molecules needed for sperm binding to the egg are exposed. Once through the coat, the sperm access the perivitelline space and eventually the egg’s plasma membrane, called the oolemma. It binds to it and both egg and sperm membranes fuse.

Although the overall fertilization process has been known for a long time, a large part of the detailed molecular mechanism is still mysterious. In 2005, Inoue et al. identified Izumo1 as the sperm-specific protein involved in egg attachment. Without Izumo1, fertilization does not occur, at least in mice. It took 9 more years to pinpoint Folr4 as the Izumo1 egg partner. Folr4 is widely conserved across mammals, including marsupials. Contrary to what its name might suggest, Folr4 is not a folate receptor, but it efficiently binds Izumo1 and hence has been renamed Juno, after Jupiter’s wife (and sister). The Juno and Izumo1 interaction is an absolute requirement for fertilization. In the absence of Juno, mice display no particular phenotype in a daily life, but are totally sterile, although they mate normally.

After fertilization, the egg becomes refractory to further sperm fusion events to prevent polyspermy. This process involves biochemical changes of the oolemma occurring 30-45 minutes after the initial fusion event, as well as hardening of the zona pellucida in a second phase. Juno may play a role in establishing the membrane block to polyspermy. Indeed, it is rapidly shed from the oolemma and redistributed to vesicles within the perivitelline space where it may create an area of “decoy eggs” to neutralize incoming sperm.

This discovery is not yet “everything you always wanted to know about” fertilization, for instance it does not unveil the fusion mechanism itself, but is nevertheless a major step forward.

As of this release, human and mouse Juno proteins have been updated in UniProtKB/Swiss-Prot.

UniProtKB news

Extension of the UniProtKB accession number format

We have extended the UniProtKB accession number format to 10 alphanumerical characters by adding a third pattern for new UniProtKB accession numbers. Old UniProtKB accession numbers will not change. The valid patterns for UniProtKB accession numbers are:


The three patterns can be combined into the following regular expression:


Changes to the controlled vocabulary for PTMs

New term for the feature key ‘Modified residue’ (‘MOD_RES’ in the flat file):

  • N6-glutaryllysine

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