Drosophila Importin α1 Performs Paralog-Specific Functions Essential For Gametogenesis

• Published in: Genetics (Austin) 2008-02, Vol.178 (2), p.839-850
• Main Authors: Ratan, R, Mason, D A, Sinnot, B, Goldfarb, D S, Fleming, R J
• Format: Article
• Language: English
• Subjects: Investigations
• ISSN: 1943-2631; 0016-6731; 1943-2631
• DOI: 10.1534/genetics.107.081778

Importin α's mediate nuclear transport by linking nuclear localization signal (NLS)-containing proteins to importin β1. Animal genomes encode three conserved groups of importin α's, α1's, α2's, and α3's, each of which are competent to bind classical NLS sequences. Using Drosophila melanogaster we describe the isolation and phenotypic characterization of the first animal importin α1 mutant. Animal α1's are more similar to ancestral plant and fungal α1-like genes than to animal α2 and α3 genes. Male and female importin α1 (Dα1) null flies developed normally to adulthood (with a minor wing defect) but were sterile with defects in gametogenesis. The Dα1 mutant phenotypes were rescued by Dα1 transgenes, but not by Dα2 or Dα3 transgenes. Genetic interactions between the ectopic expression of Dα1 and the karyopherins CAS and importin β1 suggest that high nuclear levels of Dα1 are deleterious. We conclude that Dα1 performs paralog-specific activities that are essential for gametogenesis and that regulation of subcellular Dα1 localization may affect cell fate decisions. The initial expansion and specialization of the animal importin α-gene family may have been driven by the specialized needs of gametogenesis. These results provide a framework for studies of the more complex mammalian importin α-gene family.