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

Nuclear pore complexes, critical for nucleocytoplasmic transport, are composed of nucleoporins (Nups). Recent studies have uncovered roles for different Nups in processes like cellular differentiation, contributing richly to organismal development. Intriguingly, the Nup107 complex member, Nup43, is linked with premature ovarian insufficiency (POI) in humans. We report that Nup43 is integral to the maintenance of Drosophila fertility. Nup43 null mutant ( Nup43 ^KO ) generated by CRISPR-Ca9 causes sterility in both females and males. While oocyte development is halted at the first division stage, the Nup43 ^KO males are sterile due to defective spermatogenesis, which is arrested at the canoe stage of development in Nup43 ^KO mutants. The nuclear elongation, shaping, and actin cone formation steps of individualization complex (IC) formation are adversely affected, suspending sperm maturation. All these defects were rescued by the expression of the Nup43 transgene in null mutants, suggesting the criticality of Nup43 function in spermatogenesis. Myosin VI (jar), an actin cone modulator, and Nup43 interactor can partially rescue the actin cone formation but not the sterility defects. We propose that Nup43 facilitates sperm individualization along with jar by promoting actin cone formation during spermatogenesis. These observations uncover a novel yet critical function for Nup43 in Drosophila gonad development and spermatogenesis.