The Drosophila Embargoed Gene is Required for Larval Progression and Encodes the Functional Homolog of Schizosaccharomyces Crm1

Overview

Journal Genetics

Publisher Oxford University Press

Specialty Genetics

Date 2000 Aug 5

PMID 10924475

Citations 17

Authors

S Collier

H Y Chan

T Toda

C McKimmie

G Johnson

P N Adler

C OKane

M Ashburner

Affiliations

Soon will be listed here.

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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References

Torok 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; 135(1):71-80. PMC: 1205628. DOI: 10.1093/genetics/135.1.71. View

Davis I . Nuclear polarity and nuclear trafficking in Drosophila. Semin Cell Dev Biol. 1997; 8(1):91-7. DOI: 10.1006/scdb.1996.0126. View

Ohno M, Fornerod M, Mattaj I . Nucleocytoplasmic transport: the last 200 nanometers. Cell. 1998; 92(3):327-36. DOI: 10.1016/s0092-8674(00)80926-5. View

Bachelerie F, Dargemont C . Evidence for a role of CRM1 in signal-mediated nuclear protein export. Science. 1997; 278(5335):141-4. DOI: 10.1126/science.278.5335.141. View

Toda T, Shimanuki M, Saka Y, Yamano H, Adachi Y, Shirakawa M . Fission yeast pap1-dependent transcription is negatively regulated by an essential nuclear protein, crm1. Mol Cell Biol. 1992; 12(12):5474-84. PMC: 360485. DOI: 10.1128/mcb.12.12.5474-5484.1992. View

Fukuda M, Asano S, Nakamura T, Adachi M, Yoshida M, Yanagida M . CRM1 is responsible for intracellular transport mediated by the nuclear export signal. Nature. 1997; 390(6657):308-11. DOI: 10.1038/36894. View

Brown N, Kafatos F . Functional cDNA libraries from Drosophila embryos. J Mol Biol. 1988; 203(2):425-37. DOI: 10.1016/0022-2836(88)90010-1. View

Hamilton B, Palazzolo M, Chang J, VijayRaghavan K, Mayeda C, Whitney M . Large scale screen for transposon insertions into cloned genes. Proc Natl Acad Sci U S A. 1991; 88(7):2731-5. PMC: 51312. DOI: 10.1073/pnas.88.7.2731. View

Toone W, Kuge S, Samuels M, Morgan B, 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; 12(10):1453-63. PMC: 316839. DOI: 10.1101/gad.12.10.1453. View

10.

Altschul S, Gish W, Miller W, Myers E, Lipman D . Basic local alignment search tool. J Mol Biol. 1990; 215(3):403-10. DOI: 10.1016/S0022-2836(05)80360-2. View

11.

Turi T, Webster P, Rose J . Brefeldin A sensitivity and resistance in Schizosaccharomyces pombe. Isolation of multiple genes conferring resistance. J Biol Chem. 1994; 269(39):24229-36. View

12.

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; 108(4):1195-207. PMC: 2115495. DOI: 10.1083/jcb.108.4.1195. View

13.

Maundrell K . Thiamine-repressible expression vectors pREP and pRIP for fission yeast. Gene. 1993; 123(1):127-30. DOI: 10.1016/0378-1119(93)90551-d. View

14.

Collier S, Gubb D . Drosophila tissue polarity requires the cell-autonomous activity of the fuzzy gene, which encodes a novel transmembrane protein. Development. 1997; 124(20):4029-37. DOI: 10.1242/dev.124.20.4029. View

15.

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; 250(1):59-68. DOI: 10.1007/BF02191825. View

16.

Schonbaum C, Organ E, Qu S, Cavener D . The Drosophila melanogaster stranded at second (sas) gene encodes a putative epidermal cell surface receptor required for larval development. Dev Biol. 1992; 151(2):431-45. DOI: 10.1016/0012-1606(92)90183-h. View

17.

Fornerod M, Ohno M, Yoshida M, Mattaj I . CRM1 is an export receptor for leucine-rich nuclear export signals. Cell. 1997; 90(6):1051-60. DOI: 10.1016/s0092-8674(00)80371-2. View

18.

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; 13(8):946-53. PMC: 316640. DOI: 10.1101/gad.13.8.946. View

19.

Fasken M, Saunders R, Rosenberg M, Brighty D . A leptomycin B-sensitive homologue of human CRM1 promotes nuclear export of nuclear export sequence-containing proteins in Drosophila cells. J Biol Chem. 2000; 275(3):1878-86. DOI: 10.1074/jbc.275.3.1878. View

20.

Yang J, Bardes E, Moore J, Brennan J, Powers M, Kornbluth S . Control of cyclin B1 localization through regulated binding of the nuclear export factor CRM1. Genes Dev. 1998; 12(14):2131-43. PMC: 317017. DOI: 10.1101/gad.12.14.2131. View