The molecular complexity of fertilization: Introducing the concept of a fertilization synapse

Abstract

The details of sperm-egg interactions remain a relative mystery despite many decades of research. As new molecular complexities are being discovered, we need to revise the framework in which we think about fertilization. As such, we propose that fertilization involves the formation of a synapse between the sperm and egg. A cellular synapse is a structure that mediates cell adhesion, signaling, and secretion through specialized zones of interaction and polarity. In this review, we draw parallels between the immune synapse and fertilization, and argue that we should consider sperm-egg recognition, binding, and fusion in the context of a "fertilization synapse." Mol. Reprod. Dev. 83: 376-386, 2016. © 2016 Wiley Periodicals, Inc.

Figure 1

Molecular components of the immune and fertilization synapses. A) Components and organization of a stable immune synapse. The TCR is centrally clustered in the central supramolecular activation cluster (cSMAC), along with coreceptors and costimulatory molecules such as CD3, CD4 and CD28. The cSMAC is surrounded by the peripheral supramolecular activation cluster (pSMAC) containing LFA-1. Reports differ in the localization of CD2 and partner molecules to the cSMAC or pSMAC (Dustin et al., 1998; Dustin, 2014). Figure based on Friedl et al., 2005 and Dustin, 2014. B) Proteins on the surface of sperm and egg that are genetically verified to be essential for fertilization in C. elegans. At present, no known binding pairs between sperm and egg have been identified in this system. The spatial organization of these proteins at the site of fertilization also requires further investigation. C) Proteins involved in mammalian fertilization. IZUMO1 and JUNO form the only sperm-egg binding pair identified in mammals to date. Genetic data also shows essential roles for CD9 on the egg and SPACA6 on the sperm. Figure based on Schultz and Williams, 2005 and Inoue et al., 2015. See text for additional details.