CaMKIIalpha interacts with multi-PDZ domain protein MUPP1 in spermatozoa and prevents spontaneous acrosomal exocytosis

The success of acrosomal exocytosis, a complex process with a variety of inter-related steps, relies on the coordinated interaction of participating signaling molecules. Since the acrosome reaction resembles Ca(2+)-regulated exocytosis in neurons, we investigated whether cognate neuronal binding partners of the multi-PDZ domain protein MUPP1, which recruits molecules that control the initial tethering and/or docking between the acrosomal vesicle and the plasma membrane, are also expressed in spermatozoa, and whether they contribute to the regulation of acrosomal secretion. We observed that CaMKIIalpha colocalizes with MUPP1 in the acrosomal region of epididymal spermatozoa where the kinase selectively binds to a region encompassing PDZ domains 10-11 of MUPP1. Furthermore, we found that pre-treating mouse spermatozoa with a CaMKII inhibitor that directly blocks the catalytic region of the kinase, as well as a competitive displacement of CaMKIIalpha from PDZ domains 10-11, led to a significant increase in spontaneous acrosomal exocytosis. Since Ca(2+)-calmodulin releases CaMKIIalpha from the PDZ scaffolding protein, MUPP1 represents a central signaling platform to dynamically regulate the assembly and disassembly of binding partners pertinent to acrosomal secretion, thereby precisely adjusting an increase in Ca(2+) to synchronized fusion pore formation

The “acrosomal synapse”: Subcellular organization by lipid rafts and scaffolding proteins exhibits high similarities in neurons and mammalian spermatozoa

Mammalian spermatozoa are highly polarized cells composed of two morphological and functional units, each optimized for a special task. Although the apparent division into head and tail may as such represent the anatomical basis to avoid random diffusion of their special sets of signaling proteins and lipids, recent findings demonstrate the presence of lipid raft-derived membrane platforms and specific scaffolding proteins, thus indicating that smaller sub-domains exist in the two functional units of male germ cells. The aim of this review is to summarize new insights into the principles of subcellular organization in mammalian spermatozoa. Special emphasis is placed on recent observations indicating that an “acrosomal synapse” is formed by lipid raft-derived membrane micro-environments and multidomain scaffolding proteins. Both mechanisms appear to be responsible for ensuring the attachment of the huge acrosomal vesicle to the overlaying plasma membrane, as well as for preventing an accidental spontaneous loss of the single acrosome