Essential role for Nup43 in Drosophila fertility and spermiogenesis through Myosin VI-dependent actin cone assembly dynamics

Nuclear pore complexes, composed of nucleoporins (Nups), are critical for bidirectional nucleocytoplasmic transport. Studies on Nups have linked them with various cellular processes, including cell division, contributing significantly to organismal development. Intriguingly, Nup43, an integral member of Nup107 complex, is linked with premature ovarian insufficiency in humans. Here, we report that Nup43 is integral to the maintenance of Drosophila fertility. Both the females and males of Nup43 null mutant are sterile. In Nup43 mutants, embryonic development is halted at the first division stage, and males are sterile due to an arrest at the canoe stage of spermiogenesis. The nuclear elongation, shaping, and actin cone assembly steps of individualization complex formation are adversely affected, suspending sperm maturation. Expression through Nup43 transgene in Nup43 null mutants completely rescues spermiogenesis defects. Actin-based motor, Myosin VI (jar), interacts with Nup43 and rescues the actin cone assembly but not the sterility defects. We have uncovered a novel non-canonical function for Nup43 in Drosophila spermiogenesis, and propose that Nup43, along with jar, facilitates sperm individualization by promoting actin cone assembly.