nup154 Genetically Interacts With cup and Plays a Cell-Type-Specific Function During Drosophila melanogaster Egg-Chamber Development

Abstract

Nucleoporin Nup154 is a Drosophila component of the nuclear pore complex (NPC), evolutionarily conserved from yeast to humans. While functional studies carried out in both yeast and metazoan cells indicated that Nup154 homologs are key elements of the NPC framework, the striking phenotypic specificity displayed by nup154 hypomorphic mutant alleles suggested that Nup154 might play additional roles in the context of the NPC. Actually, genetic analyses demonstrated that mutant nurse-cell nuclei do not undergo a normal chromosome dispersal process, uncovering an essential requirement for nup154 gene function during oogenesis. In this report, we show that Nup154 interacts genetically and physically with Cup, a germline-specific protein implicated in multiple aspects of female gametogenesis, including the regulation of the nurse-cell chromosome structure. The two proteins colocalize in vivo and are coimmunoprecipitated from ovarian extracts. Moreover, cup, nup154 double mutants exhibit much stronger oogenesis defects than single mutants. Our findings delineate an intriguing scenario where an ubiquitous nucleoporin might directly influence specialized developmental events.

A feedback loop betweenWolbachiaand theDrosophila gurkenmRNP complex influencesWolbachiatiter

“…Furthermore, Sqd binds Cup, a translational repressor that is required for localization of grk (Clouse et al, 2008). Cup has been shown to interact with Nup154, a member of a protein family that supports nuclear pore assembly and nuclear import processes (Grimaldi et al, 2007). This scenario provides another route by which grk mRNPs might affect availability of host products relevant to Wolbachia titer regulation.…”

TheC. eleganshomolog of nucleoporin Nup98 is required for the integrity and function of germline P granules

“…GFP::NPP-8 did localize to P granules but we were unable to verify this localization for endogenous NPP-8. Interestingly, the Drosophila NPP-8 homolog (Nup154) has also been reported to localize to cytoplasmic complexes when expressed as a GFP fusion in germ cells (Grimaldi et al, 2007). Consistent with NPP-8 and CeNup98 functioning together, the corresponding yeast homologs Nup157 and Nup145N have been reported to form a complex in vitro and in vivo (Lutzmann et al, 2005).…”

Dynamics and diverse functions of nuclear pore complex proteins

“…78,79 Consequently, hypomorphic mutations in Nup154 cause male and female sterility and reduction of cell proliferation in the adult fly. 78 Whereas Nup154 function during gametogenesis involves its association with Cup, a key player in female germ-line development in Drosophila, 78 Nup154 function during spermatogenesis is linked to TGF-β signaling.…”

“…78,79 Consequently, hypomorphic mutations in Nup154 cause male and female sterility and reduction of cell proliferation in the adult fly. 78 Whereas Nup154 function during gametogenesis involves its association with Cup, a key player in female germ-line development in Drosophila, 78 Nup154 function during spermatogenesis is linked to TGF-β signaling. In testes and in cultured Drosophila cell lines, depletion of Nup154 prevented nuclear accumulation of Mad (mothers against decapentaplegic; mammalian Smad1) and Medea (mammalian Smad4), 80 two Smad-like signal transducers in Drosophila.…”

“…96 Hypomorphic mutant alleles of Nup154 affect female and male fertility in Drosophila (see above). 78,79,99 Mutations in Nup155, the human homolog of Nup154, are associated with atrial fibrillation (AF), the most common form of sustained clinical arrhythmia. 100 While homozygous Nup155 −/− mice die during embryonic development, heterozygous Nup155 +/− mice show an AF phenotype.…”