Nup154, a New Drosophila Gene Essential for Male and Female Gametogenesis Is Related to the Nup155 Vertebrate Nucleoporin Gene

Abstract

The Nup154 gene of Drosophila encodes a protein showing similarity with known nucleoporins: rat Nup155 and yeast Nup170 and Nup157. Hypomorphic mutant alleles of Nup154 affected female and male fertility, allowing investigation of the gene function in various steps of oogenesis and spermatogenesis. Nup154 was required in testes for cyst formation, control of spermatocyte proliferation and meiotic progression. In ovaries, Nup154 was essential for egg chamber development and oocyte growth. In both the male and female germ line, as well as in several other cell types, the Nup154 protein was detected at the nuclear membrane, but was also present inside the nucleus. Intranuclear localization has not previously been described for rat Nup155 or yeast Nup170 and Nup157. In mutant egg chambers the Nup154 protein accumulated in the cytoplasm, while it was only barely detected at the nuclear envelopes. FG repeats containing nucleoporins detected with mAb414 antibody were also mislocalized to a certain extent in Nup154 mutant alleles. This suggests that Nup154 could be required for localizing other nucleoporins within the nuclear pore complex, as previously demonstrated for the yeast Nup170. On the other hand, no evident defects in lamin localization were observed, indicating that Nup155 mutations did not affect the overall integrity of the nuclear envelope. However, ultrastructural analyses revealed that in mutant cells the morphology of the nuclear envelope was altered near the nuclear pore complexes. Finally, the multiplicity of phenotypes observed in Nup154 mutant alleles suggests that this gene plays a crucial role in cell physiology.

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

“…These data indicate that the biological relevance of this group of evolutionarily conserved core elements of the NPC is greater than previously thought. The finding that Nup154 is essential for gametogenesis in both sexes not only supports this notion, but also raises the question of whether this nucleoporin might have acquired celltype-specific functional features (Gigliotti et al 1998;Kiger et al 1999).…”

“…Twothirds of them, to different extents, have been conserved in evolution, suggesting that they might share critical structural and/or functional features (reviewed in Suntharalingam and Wente 2003). One group of highly related nucleoporins comprises S. cerevisiae Nup170 and Nup157, Drosophila Nup154, and mammalian Nup155 (Radu et al 1993;Aitchison et al 1995;Gigliotti et al 1998). Initially depicted as structural proteins, these nucleoporins have more recently revealed very interesting roles in the regulation of both NPC assembly and function.…”

Defects in nuclear transport enhanceSegregation Distortion

“…54,16 Mutations in both importin α2 and Fs(2)Ket, which normally encodes importin β, 27 also enhance distortion. Mutations in Nup 154, a nucleoporin, 34 and cas, which normally encodes an exporter of importins, 55 show very mild distortion. It was possible that the Nup 214 mutation caused more distortion than was being measured because its chromosome also carries an Rsp ss allele, and that could artificially inflate the number of male offspring counted.…”

“…The allele studied was a hypomorphic mutation, but had strong effects on gametogenesis. 34 It may be germ-line specific in its function and thus have a greater negative effect on nuclear transport in testes than other nucleoporins.…”

Genome-wide patterns of natural variation reveal strong selective sweeps and ongoing genomic conflict in Drosophila mauritiana

“…Nup154 is significant in the unpolarized test with D. melanogaster at FDR 0.1 and at FDR 0.001 with D. yakuba as outgroup. Nup154 is a conserved nucleoporin essential for viability (Kiger et al 1999) and crucial for normal oogenesis and spermatogenesis (Gigliotti et al 1998;Colozza et al 2011), and interacts with CG8771 and CG11943 (Jensen et al 2009), homologs of the human NUP188 and NUP205 genes, respectively. Nup160, a hybrid lethality gene between D. simulans and D. melanogaster (Tang and Presgraves 2009), is significant at FDR 0.01 (FDR 0.001) in the unpolarized test with D. melanogaster (D. yakuba) as reference, and Nup133 at FDR 0.1 in the polarized test (Supplemental Tables S5-S7).…”