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. 2000 Aug;155(4):1799–1807. doi: 10.1093/genetics/155.4.1799

The Drosophila embargoed gene is required for larval progression and encodes the functional homolog of schizosaccharomyces Crm1.

S Collier 1, H Y Chan 1, T Toda 1, C McKimmie 1, G Johnson 1, P N Adler 1, C O'Kane 1, M Ashburner 1
PMCID: PMC1461193  PMID: 10924475

Abstract

The CRM1 (Exportin 1) protein is a receptor for leucine-rich nuclear export signal sequences. We have molecularly characterized the Drosophila melanogaster embargoed (emb) gene and find that it encodes a product with 49 and 71% sequence identity to the fission yeast Schizosaccharomyces pombe and human CRM1 proteins, respectively. We show that expression of the emb cDNA is sufficient to suppress the growth phenotype of both conditional-lethal and null S. pombe crm1(-) mutant strains, suggesting that emb encodes the functional homologue of the S. pombe Crm1 protein. Through mutagenesis screens we have recovered a series of recessive lethal emb mutations. There is a substantial maternal contribution of emb mRNA and animals hemizygous for our emb alleles can develop to second instar larvae but persist at this stage and consistently fail to undergo the molt to the third instar stage. We see a nuclear accumulation of endogenous actin in the intestinal epithelial cells of the emb mutant larvae, consistent with a role for the emb gene product in nuclear export of actin protein.

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Selected References

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  1. Adachi Y., Yanagida M. Higher order chromosome structure is affected by cold-sensitive mutations in a Schizosaccharomyces pombe gene crm1+ which encodes a 115-kD protein preferentially localized in the nucleus and its periphery. J Cell Biol. 1989 Apr;108(4):1195–1207. doi: 10.1083/jcb.108.4.1195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Altschul S. F., Gish W., Miller W., Myers E. W., Lipman D. J. Basic local alignment search tool. J Mol Biol. 1990 Oct 5;215(3):403–410. doi: 10.1016/S0022-2836(05)80360-2. [DOI] [PubMed] [Google Scholar]
  3. Berthelsen J., Kilstrup-Nielsen C., Blasi F., Mavilio F., Zappavigna V. The subcellular localization of PBX1 and EXD proteins depends on nuclear import and export signals and is modulated by association with PREP1 and HTH. Genes Dev. 1999 Apr 15;13(8):946–953. doi: 10.1101/gad.13.8.946. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brown N. H., Kafatos F. C. Functional cDNA libraries from Drosophila embryos. J Mol Biol. 1988 Sep 20;203(2):425–437. doi: 10.1016/0022-2836(88)90010-1. [DOI] [PubMed] [Google Scholar]
  5. Collier S., Gubb D. Drosophila tissue polarity requires the cell-autonomous activity of the fuzzy gene, which encodes a novel transmembrane protein. Development. 1997 Oct;124(20):4029–4037. doi: 10.1242/dev.124.20.4029. [DOI] [PubMed] [Google Scholar]
  6. Davis I. Nuclear polarity and nuclear trafficking in Drosophila. Semin Cell Dev Biol. 1997 Feb;8(1):91–97. doi: 10.1006/scdb.1996.0126. [DOI] [PubMed] [Google Scholar]
  7. Fasken M. B., Saunders R., Rosenberg M., Brighty D. W. A leptomycin B-sensitive homologue of human CRM1 promotes nuclear export of nuclear export sequence-containing proteins in Drosophila cells. J Biol Chem. 2000 Jan 21;275(3):1878–1886. doi: 10.1074/jbc.275.3.1878. [DOI] [PubMed] [Google Scholar]
  8. Fornerod M., Ohno M., Yoshida M., Mattaj I. W. CRM1 is an export receptor for leucine-rich nuclear export signals. Cell. 1997 Sep 19;90(6):1051–1060. doi: 10.1016/s0092-8674(00)80371-2. [DOI] [PubMed] [Google Scholar]
  9. Fukuda M., Asano S., Nakamura T., Adachi M., Yoshida M., Yanagida M., Nishida E. CRM1 is responsible for intracellular transport mediated by the nuclear export signal. Nature. 1997 Nov 20;390(6657):308–311. doi: 10.1038/36894. [DOI] [PubMed] [Google Scholar]
  10. Hamilton B. A., Palazzolo M. J., Chang J. H., VijayRaghavan K., Mayeda C. A., Whitney M. A., Meyerowitz E. M. Large scale screen for transposon insertions into cloned genes. Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2731–2735. doi: 10.1073/pnas.88.7.2731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Ito H., Fukuda Y., Murata K., Kimura A. Transformation of intact yeast cells treated with alkali cations. J Bacteriol. 1983 Jan;153(1):163–168. doi: 10.1128/jb.153.1.163-168.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kumada K., Yanagida M., Toda T. Caffeine-resistance in fission yeast is caused by mutations in a single essential gene, crm1+. Mol Gen Genet. 1996 Jan 15;250(1):59–68. doi: 10.1007/BF02191825. [DOI] [PubMed] [Google Scholar]
  13. Maundrell K. Thiamine-repressible expression vectors pREP and pRIP for fission yeast. Gene. 1993 Jan 15;123(1):127–130. doi: 10.1016/0378-1119(93)90551-d. [DOI] [PubMed] [Google Scholar]
  14. Nishi K., Yoshida M., Fujiwara D., Nishikawa M., Horinouchi S., Beppu T. Leptomycin B targets a regulatory cascade of crm1, a fission yeast nuclear protein, involved in control of higher order chromosome structure and gene expression. J Biol Chem. 1994 Mar 4;269(9):6320–6324. [PubMed] [Google Scholar]
  15. Ohno M., Fornerod M., Mattaj I. W. Nucleocytoplasmic transport: the last 200 nanometers. Cell. 1998 Feb 6;92(3):327–336. doi: 10.1016/s0092-8674(00)80926-5. [DOI] [PubMed] [Google Scholar]
  16. Ossareh-Nazari B., Bachelerie F., Dargemont C. Evidence for a role of CRM1 in signal-mediated nuclear protein export. Science. 1997 Oct 3;278(5335):141–144. doi: 10.1126/science.278.5335.141. [DOI] [PubMed] [Google Scholar]
  17. Schonbaum C. P., Organ E. L., Qu S., Cavener D. R. The Drosophila melanogaster stranded at second (sas) gene encodes a putative epidermal cell surface receptor required for larval development. Dev Biol. 1992 Jun;151(2):431–445. doi: 10.1016/0012-1606(92)90183-h. [DOI] [PubMed] [Google Scholar]
  18. Toda T., Shimanuki M., Saka Y., Yamano H., Adachi Y., Shirakawa M., Kyogoku Y., Yanagida M. Fission yeast pap1-dependent transcription is negatively regulated by an essential nuclear protein, crm1. Mol Cell Biol. 1992 Dec;12(12):5474–5484. doi: 10.1128/mcb.12.12.5474. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Toone W. M., Kuge S., Samuels M., Morgan B. A., Toda T., Jones N. Regulation of the fission yeast transcription factor Pap1 by oxidative stress: requirement for the nuclear export factor Crm1 (Exportin) and the stress-activated MAP kinase Sty1/Spc1. Genes Dev. 1998 May 15;12(10):1453–1463. doi: 10.1101/gad.12.10.1453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Turi T. G., Webster P., Rose J. K. Brefeldin A sensitivity and resistance in Schizosaccharomyces pombe. Isolation of multiple genes conferring resistance. J Biol Chem. 1994 Sep 30;269(39):24229–24236. [PubMed] [Google Scholar]
  21. Török T., Tick G., Alvarado M., Kiss I. P-lacW insertional mutagenesis on the second chromosome of Drosophila melanogaster: isolation of lethals with different overgrowth phenotypes. Genetics. 1993 Sep;135(1):71–80. doi: 10.1093/genetics/135.1.71. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Wada A., Fukuda M., Mishima M., Nishida E. Nuclear export of actin: a novel mechanism regulating the subcellular localization of a major cytoskeletal protein. EMBO J. 1998 Mar 16;17(6):1635–1641. doi: 10.1093/emboj/17.6.1635. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Yang J., Bardes E. S., Moore J. D., Brennan J., Powers M. A., Kornbluth S. Control of cyclin B1 localization through regulated binding of the nuclear export factor CRM1. Genes Dev. 1998 Jul 15;12(14):2131–2143. doi: 10.1101/gad.12.14.2131. [DOI] [PMC free article] [PubMed] [Google Scholar]

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