The mammalian acrosome reaction: Gateway to sperm fusion with the oocyte?

Abstract

Mammalian sperm undergo discharge of a single, anterior secretory granule following their attachment to the zona pellucida surrounding the oocyte. This secretory discharge is known for historical reasons as the acrosome reaction. It fulfils a number of purposes and without it, sperm are unable to penetrate the zona pellucida and fuse with the oocyte. In this review, we focus on the role of the acrosome reaction in the development of fusion competence in sperm. Any naturally occurring membrane fusion has two major sequential steps: a docking or adhesion step, in which two membranes adhere, and a fusion step, in which their lipid bilayers are destabilized and merged and a cellular compartment is either created or destroyed. Recent evidence suggests that there is an important role for oocyte integrins and sperm-bound disintegrins in mammalian sperm/oocyte adhesion and fusion. The fusion mechanism employed by sperm remains poorly understood, however, and circumstantial evidence suggests it is more complex than the interaction between a single protein species and its target. Sperm/oocyte fusion is probably the most accessible eukaryotic model for intercellular fusion currently available, partly because it is temporally separated from gene expression. Elucidation of the mechanism of sperm/oocyte fusion may throw light on the mechanism of other intercellular fusions such as myoblast fusion, and the evolutionary relationship of intercellular membrane fusion to intracellular membrane fusion.

Exposure of Sperm Head Equatorin after Acrosome Reaction and Its Fate after Fertilization in Mice1

“…Although these observations highlight our earlier expectations that equatorin may diffuse outside and associate with the equatorial plasma membrane rendering it fusible with the oocyte microvilli [21,43], it has yet to be seen whether similar events occur in zona-penetrated spermatozoa. There are some other circumstantial evidences to support equatorial relocation of fusogenic proteins after acrosome reaction [24,[44][45][46].…”

Structural modification of the hamster sperm acrosome during posttesticular development in the epididymis

“…For example, in guinea pig spermatozoa the apical segment of the acrosome displays three structurally distinct domains, termed the M1, M2, and M3 regions (Westbrook-Case et al, 1994, 1995Yoshinaga et al, 1998) which possess specific protein components (Foster et al, 1997;Talbot and DiCarlantonio, 1985;WestbrookCase et al, 1995;Yoshinaga et al, 2001). Biochemical and ultrastructural analyses of guinea pig spermatozoa examined during the course of the acrosome reaction demonstrate both a temporally regulated release of acrosomal proteins and a sequential disassembly of specific structural domains of the apical segment (DiCarlantonio and Talbot, 1988;Green, 1978;Kim et al, 2001b) suggesting that compartmentalization and/or acrosomal matrix interaction controls sequential protein release (Allen and Green, 1997;Hardy et al, 1991;Huang et al, 1985). These findings have been confirmed by biochemical studies demonstrating that, whereas some acrosomal proteins are highly soluble and readily released upon acrosome disruption, others remain in a particulate fraction being associated with an insoluble framework termed the acrosomal matrix (Hardy et al, 1991;Olson et al, 1988).…”

The Multi‐PDZ domain protein MUPP1 as a lipid raft‐associated scaffolding protein controlling the acrosome reaction in mammalian spermatozoa

“…During this unique process of exocytosis, called the acrosome reaction (AR), fusion between the outer acrosomal membrane and the adjacent plasma membrane of the sperm occurs at several distinct points, thereby leading to the secretion of hydrolyzing enzymes necessary for zona pellucida penetration (Allen and Green, 1997). Although acrosomal exocytosis in sperm cells differs from other known exocytotic processes, mainly because the acrosome is a single secretory vesicle, certain parallels can be drawn between the AR and membrane fusion in neurons and neuroendocrine/exocrine cells (for review see Tulsiani and Abou-Haila, 2004).…”