Gamete Binding And Fusion

Successful mammalian fertilization results in the union of two gametes, a spermatozoon and a mature oocyte. Membrane fusion events are essential for at least two distinct steps of the fertilization process: (i) the vesiculation of the acrosomal surface membranes during sperm acrosomal exocytosis (AE), induced by sperm binding to the egg-coat, and (ii) fusion of the oocyte plasma membrane, the oolemma, with the sperm plasma membrane that occurs after AE and sperm-egg coat penetration. The rearrangement of sperm plasma membrane domains/membrane lipid raft formation during sperm capacitation in the female reproductive tract is a priming step that enables the fusion and vesiculation of outer acrosomal membranes during AE. The membrane fusion/vesiculation events of AE seem to share similarities with synaptic vesicle fusion, assisted by the membrane proteins of the SNARE hypothesis. The AE exposes the transmembrane receptors on the sperm head equatorial segment in preparation for sperm-oolemma adhesion and fusion. Gene ablation studies indicate that the tetraspanin family proteins CD9 and CD81 on the oolemma interact with the superglobulin family protein IZUMO on the sperm plasmalemma to mediate sperm-oolemma adhesion in mammals. The fusogenicity of IZUMO has not been established, so the involvement of this system in the actual membrane fusion part of sperm oolemma interaction remains open. Interactions of ADAM family proteins on sperm plasma membrane with oolemma integrins appear non-essential during sperm-oolemma fusion, but integrins may play a supporting role via sustenance of the tetraspanin web in the oocyte cortex. Sperm-oolemma binding may be reinforced by a cast of other receptors found on the surface of the sperm head (e.g. CRISP and MN9). The present chapter reviews recent progress in the study of these fundamental factors of gamete membrane fusion during mammalian fertilization.