ELAPOR1 mediated vesicle traffic is required for acrosome biogenesis and male fertility in mice.

Spermiogenesis is the post-meiotic differentiation and morphological change of the haploid spermatids. Acrosome biogenesis is one of the key events of spermiogenesis, which generates a specialized membranous organelle crucial for shaping the balanced morphology of sperm head and ensuring sperm fertility. Defects in acrosome biogenesis can result in globozoospermia or teratozoospermia, causing male infertility. Although acrosome biogenesis is known to derive from the Golgi apparatus, the processes that trafficking, targeting and fusion of the Golgi-derived vesicles are yet to be fully understood. In this study, we demonstrated that ELAPOR1 abundantly expressed in spermatids was required for acrosome biogenesis during spermiogenesis. By selectively deleting Elapor1 in premeiotic germ cells, we found that ELAPOR1 deficient mice were male infertile and exhibited round-head, absence of acrosome, disorganized mitochondrial sheath and reduced sperm motility, phenotypically resembling human astheno-teratozoospermia. We further demonstrated that ELAPOR1 could recruit clathrin via the cytoplasmic adaptor-binding motif YSKL, and consequently contribute to the assembly of clathrin coated onto the vesicles derived from trans-Golgi network, which further mediated vesicle traffic and ultimately succeeded acrosome formation. Taken together, our findings revealed a novel role of ELAPOR1 in mediating the clathrin assembly and thereby involving in the transport of vesicles required for acrosome biogenesis during spermiogenesis.