Importin-alpha 3 is required at multiple stages of Drosophila development and has a role in the completion of oogenesis

The Drosophila importin-alpha 3 gene was isolated through its interaction w ith the large subunit of the DNA polymerase cu in a two-hybrid screen. The predicted protein sequence of Importin-alpha 3 is 65-66% identical to those of the human and mouse importin-alpha 3 and alpha 4 and 42.7% identical to that of Importin-alpha 2 (Oho31/Pendulin), the previously reported Drosoph ila homologue. Both Importin-alpha 3 and Importin-alpha 2 interact with sim ilar subsets of proteins in vitro, one of which is Ketel, the importin-beta homologue of Drosophila. importin-alpha 3 is an essential gene, whose enco ded protein is expressed throughout development. During early embryogenesis , Importin-alpha 3 accumulates at the nuclear membrane of cleavage nuclei, whereas after blastoderm formation it is characteristically found within th e interphase nuclei. Nuclear localisation is seen in several tissues throug hout subsequent development. During oogenesis its concentration within the nurse cell nuclei increases during stages 7-10, concomitant with a decline in levels in the oocyte nucleus. Mutation of importin-alpha 3 results in le thality throughout pupal development. Surviving females are sterile and sho w arrest of oogenesis at stages 7-10. Thus, Importin-alpha 3-mediated nucle ar transport is essential for completion of oogenesis and becomes limiting during pupal development. Since they have different expression patterns and subcellular localisation profiles, we suggest that the two importin-alpha homologues are not redundant in the context of normal Drosophila developmen t. (C) 2000 Academic Press.