Dear Editor,
The acrosome reaction (AR) in mammalian spermatozoa is a prerequisite for successful fertilization, because it leads to the release of hydrolytic enzymes from the acrosomal vesicle along with the exposure of the oocyte-recognition protein Izumo on the sperm surface (Bianchi et al., 2014). AR mainly follows the conserved principles of calcium-regulated exocytosis in neurons/neurosecretory cells, which is reflected by initial vesicle docking/priming steps and calcium-triggered SNARE-mediated membrane fusion (Tsai et al., 2012). However, there are some unique features of AR whose underlying molecular mechanisms are largely unknown: The acrosome is a single, huge vesicle whose exocytosis is realized by multipoint fusions of the outer acrosomal and sperm plasma membrane (Tsai et al., 2012). In addition, stimulating sperm with the oocyte's Zona pellucida (ZP) leads to a zipper-like progression of fusion pore formation that starts at the posterior acrosomal region and consistently proceeds in an anterograde direction, whereas the fusion is initiated at random sites following calcium ionophore treatment (Buffone et al., 2009). This directed propagation requires extraordinary temporal and spatial orchestration of individual pore-forming events. Remarkably, individual exocytotic events at neuronal synaptic junctions also require tight coordination, which is accomplished by a protein network termed cytomatrix of the active zone (CAZ), consisting of the multi-domain CAZ-proteins Munc13, RIM, RIM-BP, Liprin-α, ELKS/ERC, Piccolo/Aczonin, and Bassoon (Sudhof, 2012). Thus, we hypothesized that a CAZ-like network could also coordinate the success of sperm AR.