Neprilysin 4 controls acrosome structure and male fertility in Drosophila melanogaster

The acrosome is a highly conserved organelle located at the anterior tip of the mature sperm. It is essential to successful fertilization across species. Herein, we provide evidence that the peptidase Neprilysin 4 localizes to the acrosome during Drosophila sperm maturation and that activity of this enzyme is essential to proper acrosome structure, sperm tip partitioning and male fertility. In contrast to controls, sperm from animals with impaired Nep4 function exhibited a severely disturbed tip structure that affected intracellular and sperm surface components. These effects were secondary to structural defects in the acrosome morphology. Corresponding sperm were quickly discarded by the females, exhibited a reduced ability to fertilize eggs, and did not initiate embryonic development, even if sperm entry had occurred. This study demonstrates an essential role for a neprilysin in the structural integrity of the acrosome and the sperm tip, and thus introduces a new and crucial function of neprilysins in ensuring male fertility.