• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of geneticsGeneticsCurrent IssueInformation for AuthorsEditorial BoardSubscribeSubmit a Manuscript
Genetics. May 2002; 161(1): 157–170.
PMCID: PMC1462091

Drosophila melanogaster importin alpha1 and alpha3 can replace importin alpha2 during spermatogenesis but not oogenesis.


Importin alpha's mediate the nuclear transport of many classical nuclear localization signal (cNLS)-containing proteins. Multicellular animals contain multiple importin alpha genes, most of which fall into three conventional phylogenetic clades, here designated alpha1, alpha2, and alpha3. Using degenerate PCR we cloned Drosophila melanogaster importin alpha1, alpha2, and alpha3 genes, demonstrating that the complete conventional importin alpha gene family arose prior to the split between invertebrates and vertebrates. We have begun to analyze the genetic interactions among conventional importin alpha genes by studying their capacity to rescue the male and female sterility of importin alpha2 null flies. The sterility of alpha2 null males was rescued to similar extents by importin alpha1, alpha2, and alpha3 transgenes, suggesting that all three conventional importin alpha's are capable of performing the important role of importin alpha2 during spermatogenesis. In contrast, sterility of alpha2 null females was rescued only by importin alpha2 transgenes, suggesting that it plays a paralog-specific role in oogenesis. Female infertility was also rescued by a mutant importin alpha2 transgene lacking a site that is normally phosphorylated in ovaries. These rescue experiments suggest that male and female gametogenesis have distinct requirements for importin alpha2.

Full Text

The Full Text of this article is available as a PDF (479K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Kamei Y, Yuba S, Nakayama T, Yoneda Y. Three distinct classes of the alpha-subunit of the nuclear pore-targeting complex (importin-alpha) are differentially expressed in adult mouse tissues. J Histochem Cytochem. 1999 Mar;47(3):363–372. [PubMed]
  • Koepp DM, Wong DH, Corbett AH, Silver PA. Dynamic localization of the nuclear import receptor and its interactions with transport factors. J Cell Biol. 1996 Jun;133(6):1163–1176. [PMC free article] [PubMed]
  • Köhler M, Ansieau S, Prehn S, Leutz A, Haller H, Hartmann E. Cloning of two novel human importin-alpha subunits and analysis of the expression pattern of the importin-alpha protein family. FEBS Lett. 1997 Nov 3;417(1):104–108. [PubMed]
  • Adams MD, Celniker SE, Holt RA, Evans CA, Gocayne JD, Amanatides PG, Scherer SE, Li PW, Hoskins RA, Galle RF, et al. The genome sequence of Drosophila melanogaster. Science. 2000 Mar 24;287(5461):2185–2195. [PubMed]
  • Köhler M, Speck C, Christiansen M, Bischoff FR, Prehn S, Haller H, Görlich D, Hartmann E. Evidence for distinct substrate specificities of importin alpha family members in nuclear protein import. Mol Cell Biol. 1999 Nov;19(11):7782–7791. [PMC free article] [PubMed]
  • Andrade MA, Petosa C, O'Donoghue SI, Müller CW, Bork P. Comparison of ARM and HEAT protein repeats. J Mol Biol. 2001 May 25;309(1):1–18. [PubMed]
  • Kusano A, Staber C, Ganetzky B. Nuclear mislocalization of enzymatically active RanGAP causes segregation distortion in Drosophila. Dev Cell. 2001 Sep;1(3):351–361. [PubMed]
  • Aravind L, Watanabe H, Lipman DJ, Koonin EV. Lineage-specific loss and divergence of functionally linked genes in eukaryotes. Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11319–11324. [PMC free article] [PubMed]
  • Küssel P, Frasch M. Pendulin, a Drosophila protein with cell cycle-dependent nuclear localization, is required for normal cell proliferation. J Cell Biol. 1995 Jun;129(6):1491–1507. [PMC free article] [PubMed]
  • Azuma Y, Takio K, Tabb MM, Vu L, Nomura M. Phosphorylation of Srp1p, the yeast nuclear localization signal receptor, in vitro and in vivo. Biochimie. 1997 May;79(5):247–259. [PubMed]
  • Kutay U, Bischoff FR, Kostka S, Kraft R, Görlich D. Export of importin alpha from the nucleus is mediated by a specific nuclear transport factor. Cell. 1997 Sep 19;90(6):1061–1071. [PubMed]
  • Brand AH, Perrimon N. Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development. 1993 Jun;118(2):401–415. [PubMed]
  • Malik HS, Eickbush TH, Goldfarb DS. Evolutionary specialization of the nuclear targeting apparatus. Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13738–13742. [PMC free article] [PubMed]
  • Chomczynski P. A reagent for the single-step simultaneous isolation of RNA, DNA and proteins from cell and tissue samples. Biotechniques. 1993 Sep;15(3):532–537. [PubMed]
  • Máthé E, Bates H, Huikeshoven H, Deák P, Glover DM, Cotterill S. Importin-alpha3 is required at multiple stages of Drosophila development and has a role in the completion of oogenesis. Dev Biol. 2000 Jul 15;223(2):307–322. [PubMed]
  • Conti E, Uy M, Leighton L, Blobel G, Kuriyan J. Crystallographic analysis of the recognition of a nuclear localization signal by the nuclear import factor karyopherin alpha. Cell. 1998 Jul 24;94(2):193–204. [PubMed]
  • Matsusaka T, Imamoto N, Yoneda Y, Yanagida M. Mutations in fission yeast Cut15, an importin alpha homolog, lead to mitotic progression without chromosome condensation. Curr Biol. 1998 Sep 10;8(18):1031–1034. [PubMed]
  • de Bono M, Hodgkin J. Evolution of sex determination in caenorhabditis: unusually high divergence of tra-1 and its functional consequences. Genetics. 1996 Oct;144(2):587–595. [PMC free article] [PubMed]
  • Dockendorff TC, Tang Z, Jongens TA. Cloning of karyopherin-alpha3 from Drosophila through its interaction with the nuclear localization sequence of germ cell-less protein. Biol Chem. 1999 Nov;380(11):1263–1272. [PubMed]
  • Merrill C, Bayraktaroglu L, Kusano A, Ganetzky B. Truncated RanGAP encoded by the Segregation Distorter locus of Drosophila. Science. 1999 Mar 12;283(5408):1742–1745. [PubMed]
  • Erdélyi M, Máthé E, Szabad J. Genetic and developmental analysis of mutant Ketel alleles that identify the Drosophila importin-beta homologue. Acta Biol Hung. 1997;48(3):323–338. [PubMed]
  • Michaud N, Goldfarb DS. Most nuclear proteins are imported by a single pathway. Exp Cell Res. 1993 Sep;208(1):128–136. [PubMed]
  • Miyamoto Y, Imamoto N, Sekimoto T, Tachibana T, Seki T, Tada S, Enomoto T, Yoneda Y. Differential modes of nuclear localization signal (NLS) recognition by three distinct classes of NLS receptors. J Biol Chem. 1997 Oct 17;272(42):26375–26381. [PubMed]
  • Nachury MV, Ryder UW, Lamond AI, Weis K. Cloning and characterization of hSRP1 gamma, a tissue-specific nuclear transport factor. Proc Natl Acad Sci U S A. 1998 Jan 20;95(2):582–587. [PMC free article] [PubMed]
  • Geles KG, Adam SA. Germline and developmental roles of the nuclear transport factor importin alpha3 in C. elegans. Development. 2001 May;128(10):1817–1830. [PubMed]
  • Nadler SG, Tritschler D, Haffar OK, Blake J, Bruce AG, Cleaveland JS. Differential expression and sequence-specific interaction of karyopherin alpha with nuclear localization sequences. J Biol Chem. 1997 Feb 14;272(7):4310–4315. [PubMed]
  • Gönczy P, Matunis E, DiNardo S. bag-of-marbles and benign gonial cell neoplasm act in the germline to restrict proliferation during Drosophila spermatogenesis. Development. 1997 Nov;124(21):4361–4371. [PubMed]
  • Nakielny S, Dreyfuss G. Transport of proteins and RNAs in and out of the nucleus. Cell. 1999 Dec 23;99(7):677–690. [PubMed]
  • Peifer M, Berg S, Reynolds AB. A repeating amino acid motif shared by proteins with diverse cellular roles. Cell. 1994 Mar 11;76(5):789–791. [PubMed]
  • Görlich D, Kutay U. Transport between the cell nucleus and the cytoplasm. Annu Rev Cell Dev Biol. 1999;15:607–660. [PubMed]
  • Görlich D, Henklein P, Laskey RA, Hartmann E. A 41 amino acid motif in importin-alpha confers binding to importin-beta and hence transit into the nucleus. EMBO J. 1996 Apr 15;15(8):1810–1817. [PMC free article] [PubMed]
  • Percipalle P, Clarkson WD, Kent HM, Rhodes D, Stewart M. Molecular interactions between the importin alpha/beta heterodimer and proteins involved in vertebrate nuclear protein import. J Mol Biol. 1997 Mar 7;266(4):722–732. [PubMed]
  • Prieve MG, Guttridge KL, Munguia JE, Waterman ML. The nuclear localization signal of lymphoid enhancer factor-1 is recognized by two differentially expressed Srp1-nuclear localization sequence receptor proteins. J Biol Chem. 1996 Mar 29;271(13):7654–7658. [PubMed]
  • Herold A, Truant R, Wiegand H, Cullen BR. Determination of the functional domain organization of the importin alpha nuclear import factor. J Cell Biol. 1998 Oct 19;143(2):309–318. [PMC free article] [PubMed]
  • Prieve MG, Guttridge KL, Munguia J, Waterman ML. Differential importin-alpha recognition and nuclear transport by nuclear localization signals within the high-mobility-group DNA binding domains of lymphoid enhancer factor 1 and T-cell factor 1. Mol Cell Biol. 1998 Aug;18(8):4819–4832. [PMC free article] [PubMed]
  • Hood JK, Silver PA. Cse1p is required for export of Srp1p/importin-alpha from the nucleus in Saccharomyces cerevisiae. J Biol Chem. 1998 Dec 25;273(52):35142–35146. [PubMed]
  • Rørth P. Gal4 in the Drosophila female germline. Mech Dev. 1998 Nov;78(1-2):113–118. [PubMed]
  • Rout MP, Aitchison JD, Suprapto A, Hjertaas K, Zhao Y, Chait BT. The yeast nuclear pore complex: composition, architecture, and transport mechanism. J Cell Biol. 2000 Feb 21;148(4):635–651. [PMC free article] [PubMed]
  • Török I, Strand D, Schmitt R, Tick G, Török T, Kiss I, Mechler BM. The overgrown hematopoietic organs-31 tumor suppressor gene of Drosophila encodes an Importin-like protein accumulating in the nucleus at the onset of mitosis. J Cell Biol. 1995 Jun;129(6):1473–1489. [PMC free article] [PubMed]
  • Saitou N, Nei M. The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol. 1987 Jul;4(4):406–425. [PubMed]
  • Tsuji L, Takumi T, Imamoto N, Yoneda Y. Identification of novel homologues of mouse importin alpha, the alpha subunit of the nuclear pore-targeting complex, and their tissue-specific expression. FEBS Lett. 1997 Oct 13;416(1):30–34. [PubMed]
  • Sekimoto T, Imamoto N, Nakajima K, Hirano T, Yoneda Y. Extracellular signal-dependent nuclear import of Stat1 is mediated by nuclear pore-targeting complex formation with NPI-1, but not Rch1. EMBO J. 1997 Dec 1;16(23):7067–7077. [PMC free article] [PubMed]
  • Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, Smith HO, Yandell M, Evans CA, Holt RA, et al. The sequence of the human genome. Science. 2001 Feb 16;291(5507):1304–1351. [PubMed]
  • Sandler L, Hiraizumi Y, Sandler I. Meiotic Drive in Natural Populations of Drosophila Melanogaster. I. the Cytogenetic Basis of Segregation-Distortion. Genetics. 1959 Mar;44(2):233–250. [PMC free article] [PubMed]
  • Welch K, Franke J, Köhler M, Macara IG. RanBP3 contains an unusual nuclear localization signal that is imported preferentially by importin-alpha3. Mol Cell Biol. 1999 Dec;19(12):8400–8411. [PMC free article] [PubMed]
  • Weis K. Importins and exportins: how to get in and out of the nucleus. Trends Biochem Sci. 1998 May;23(5):185–189. [PubMed]
  • Tabb MM, Tongaonkar P, Vu L, Nomura M. Evidence for separable functions of Srp1p, the yeast homolog of importin alpha (Karyopherin alpha): role for Srp1p and Sts1p in protein degradation. Mol Cell Biol. 2000 Aug;20(16):6062–6073. [PMC free article] [PubMed]
  • Zinn K, McAllister L, Goodman CS. Sequence analysis and neuronal expression of fasciclin I in grasshopper and Drosophila. Cell. 1988 May 20;53(4):577–587. [PubMed]
  • Tokuyasu KT, Peacock WJ, Hardy RW. Dynamics of spermiogenesis in Drosophila melanogaster. II. Coiling process. Z Zellforsch Mikrosk Anat. 1972;127(4):492–525. [PubMed]

Articles from Genetics are provided here courtesy of Genetics Society of America


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...