Successful fertilization requires the sperm and egg to recognize and bind to each other in order to fuse and form a zygote. The molecular basis of fertilization is not well understood. In mammals, several cell-surface proteins were shown to be required for the interactions between the sperm and egg, with IZUMO1, an immunoglobulin (Ig) superfamily protein on the sperm, and JUNO, a GPI-anchored protein on the egg being the only known receptor pair (Bianchi, 2014). In C. elegans sperm, interactions with oocytes are mediated by the
spe-9 class of proteins, which consist of transmembrane proteins on the sperm surface. The non-redundant roles of these molecules suggest that they function with one another to form a complex, which we refer to as the fertilization synapse (Krauchunas, 2016). Here, we report the first secreted molecule in the
spe-9 class, SPE-51.
spe-51 mutant sperm display normal morphology, can activate, migrate and even outcompete self sperm, but fail to fertilize the oocytes. The predicted protein contains an Ig-like fold and a stretch of hydrophobic amino acids. Surprisingly, SPE-51 expressed in the body-wall muscle was taken up by coelomocytes, suggesting the protein is secreted rather than membrane-bound. The
spe-51 mutant sperm display cell-autonomous behavior, suggesting that this secreted protein stays associated with the sperm cell surface and functions either in cis on the sperm surface or in trans with the egg cell surface to complete fertilization. Consistently, endogenously tagged SPE-51 localizes to the surface of the spermatozoa. Our work presents the first examples of a secreted protein required for the interactions between the sperm and egg. We further show evidence that one of the molecules required for mammalian sperm-egg interactions, SOF1, is also secreted. Together, our work could serve as a paradigm for other mammalian sperm-secreted or reproductive tract-secreted proteins that coat the sperm surface and influence their survival, motility, and/or the ability to fertilize the egg.