title: Drosophila importin alpha1 performs paralog-specific functions essential for gametogenesis.
abstract: Importin alpha's mediate nuclear transport by linking nuclear localization signal (NLS)-containing proteins to importin beta1. Animal genomes encode three conserved groups of importin alpha's, alpha1's, alpha2's, and alpha3'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 alpha1 mutant. Animal alpha1's are more similar to ancestral plant and fungal alpha1-like genes than to animal alpha2 and alpha3 genes. Male and female importin alpha1 (Dalpha1) null flies developed normally to adulthood (with a minor wing defect) but were sterile with defects in gametogenesis. The Dalpha1 mutant phenotypes were rescued by Dalpha1 transgenes, but not by Dalpha2 or Dalpha3 transgenes. Genetic interactions between the ectopic expression of Dalpha1 and the karyopherins CAS and importin beta1 suggest that high nuclear levels of Dalpha1 are deleterious. We conclude that Dalpha1 performs paralog-specific activities that are essential for gametogenesis and that regulation of subcellular Dalpha1 localization may affect cell fate decisions. The initial expansion and specialization of the animal importin alpha-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 alpha-gene family.
authors.affiliation: Biology Department, Trinity College, Hartford, Connecticut 06106, USA.
authors.forename: R
authors.initials: R
authors.lastname: Ratan
authors.forename: D A
authors.initials: DA
authors.lastname: Mason
authors.forename: B
authors.initials: B
authors.lastname: Sinnot
authors.forename: D S
authors.initials: DS
authors.lastname: Goldfarb
authors.forename: R J
authors.initials: RJ
authors.lastname: Fleming
mesh_terms: D000818:Animals; D003433:Crosses, Genetic; D017931:DNA Primers; D029721:Drosophila Proteins / Q000235:genetics; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics*; D005260:Female; D005298:Fertility / Q000235:genetics; D005718:Gametogenesis / Q000235:genetics*; D017353:Gene Deletion; D008297:Male; D008540:Meiosis; D011995:Recombination, Genetic; D028901:alpha Karyopherins / Q000235:genetics*
chemical_list: D017931:DNA Primers; D029721:Drosophila Proteins; D028901:alpha Karyopherins; C087978:karyopherin alpha 2