Subcellular compartmentalization of a mouse sperm cell. (A) Schematic diagram of a murine sperm as an example of spermatozoon compartmentalization: The sperm head, with the acrosomal vesicle and the condensed nucleus and the flagellum with the mitochondrial-enriched mid-piece region, the principal piece and end piece segment are shown. The red dotted line demonstrates the separation between head and flagellum. (B) Hypothetical working model illustrating capacitation-dependent reorganization of lipid rafts in the plasma membrane of the acrosomal region. The two schematic drawings of the murine sperm head (upper and lower left part) show the distribution and size of raft plasma membrane platforms in the whole acrosomal region. In freshly ejaculated spermatozoa (upper parts) lipid rafts, enriched in sphingolipids (green) and cholesterol (blue), are uniformly distributed in the plasma membrane (pm) overlaying the whole acrosomal cap. In contrast, following capacitation (lower parts), rafts are more concentrated in a crescent shaped region of the sperm head. Following the size and location of rafts at higher magnification (right parts), it becomes obvious that rafts in the anterior region of the acrosomal cap in capacitated sperm aggregate upon maturation, thus leading to large-scale and stable raft clusters in the plasma membrane. Since lipid rafts in sperm recruit ZP-binding receptors as well as components of the SNARE-fusion machinery, this area may present the preferential site of hybrid vesicle formation during acrosomal secretion. This structural organization resembles the one at the active zone of the presynaptic terminal in neurons where neurotransmitter vesicle fusion occurs and thus may be termed “acrosomal synapse”. The cholesterol efflux from the plasma membrane during capacitation has been suggested to occur from the non-raft fraction and is illustrated by far less cholesterol molecules in the lower right part compared to the upper one. Possible lipid rafts in the outer acrosomal membrane (oam), and the tighter association between the two membranes, which has been suggested to occur upon capacitation, are not shown.