Importin-α3 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 with 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 Drosophila homologue. Both Importin-alpha 3 and Importin-alpha 2 interact with similar subsets of proteins in vitro, one of which is Ketel, the importin-beta homologue of Drosophila. importin-alpha 3 is an essential gene, whose encoded 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 the interphase nuclei. Nuclear localisation is seen in several tissues throughout 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 lethality throughout pupal development. Surviving females are sterile and show arrest of oogenesis at stages 7-10. Thus, Importin-alpha 3-mediated nuclear 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 development. (C) 2000 Academic Press.