Dynamic localization of the nuclear import receptor and its interactions with transport factors

doi:10.1083/jcb.133.6.1163

This Article

	Full Text (PDF, 4186K)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JCB
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Koepp, D. M.
	Articles by Silver, P. A.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Koepp, D. M.
	Articles by Silver, P. A.


Social Bookmarking

	What's this?

ARTICLES

Dynamic localization of the nuclear import receptor and its interactions with transport factors

DM Koepp, DH Wong, AH Corbett and PA Silver
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA.

Characterization of the interactions between soluble factors required for nuclear transport is key to understanding the process of nuclear trafficking. Using a synthetic lethal screen with the rna1-1 strain, we have identified a genetic interaction between Rna1p, a GTPase activating protein required for nuclear transport, and yeast importin- beta, a component of the nuclear localization signal receptor. By the use of fusion proteins, we demonstrate that Rna1p physically interacts with importin-beta. Mutants in importin-beta exhibit in vivo nuclear protein import defects, and importin-beta localizes to the nuclear envelope along with other proteins associated with the nuclear pore complex. In addition, we present evidence that importin-alpha, but not importin-beta, mislocalizes to the nucleus in cells where the GTPase Ran is likely to be in the GDP-bound state. We suggest a model of nuclear transport in which Ran-mediated hydrolysis of GTP is necessary for the import of importin-alpha and the nuclear localization signal- bearing substrate into the nucleus, while exchange of GDP for GTP on Ran is required for the export of both mRNA and importin-alpha from the nucleus.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Facebook Add to Reddit Reddit Add to Technorati Technorati Twitter What's this?

This article has been cited by other articles:

Streckfuss-Bomeke, K., Schulze, F., Herzog, B., Scholz, E., Braus, G. H. (2009). Degradation of Saccharomyces cerevisiae Transcription Factor Gcn4 Requires a C-Terminal Nuclear Localization Signal in the Cyclin Pcl5. Eukaryot Cell 8: 496-510 [Abstract] [Full Text]
McLane, L. M., Pulliam, K. F., Devine, S. E., Corbett, A. H. (2008). The Ty1 integrase protein can exploit the classical nuclear protein import machinery for entry into the nucleus. Nucleic Acids Res 36: 4317-4326 [Abstract] [Full Text]
Balzer, R. J., Henry, M. F. (2008). Snu56p Is Required for Mer1p-Activated Meiotic Splicing. Mol. Cell. Biol. 28: 2497-2508 [Abstract] [Full Text]
Fries, T., Betz, C., Sohn, K., Caesar, S., Schlenstedt, G., Bailer, S. M. (2007). A Novel Conserved Nuclear Localization Signal Is Recognized by a Group of Yeast Importins. J. Biol. Chem. 282: 19292-19301 [Abstract] [Full Text]
Ao, Z., Huang, G., Yao, H., Xu, Z., Labine, M., Cochrane, A. W., Yao, X. (2007). Interaction of Human Immunodeficiency Virus Type 1 Integrase with Cellular Nuclear Import Receptor Importin 7 and Its Impact on Viral Replication. J. Biol. Chem. 282: 13456-13467 [Abstract] [Full Text]
Spiller, M. P., Boon, K.-L., Reijns, M. A. M., Beggs, J. D. (2007). The Lsm2-8 complex determines nuclear localization of the spliceosomal U6 snRNA. Nucleic Acids Res 35: 923-929 [Abstract] [Full Text]
Luthra, R., Kerr, S. C., Harreman, M. T., Apponi, L. H., Fasken, M. B., Ramineni, S., Chaurasia, S., Valentini, S. R., Corbett, A. H. (2007). Actively Transcribed GAL Genes Can Be Physically Linked to the Nuclear Pore by the SAGA Chromatin Modifying Complex. J. Biol. Chem. 282: 3042-3049 [Abstract] [Full Text]
Goffin, L., Vodala, S., Fraser, C., Ryan, J., Timms, M., Meusburger, S., Catimel, B., Nice, E. C., Silver, P. A., Xiao, C.-Y., Jans, D. A., Gething, M.-J. H. (2006). The Unfolded Protein Response Transducer Ire1p Contains a Nuclear Localization Sequence Recognized by Multiple beta Importins. Mol. Biol. Cell 17: 5309-5323 [Abstract] [Full Text]
Hodel, A. E., Harreman, M. T., Pulliam, K. F., Harben, M. E., Holmes, J. S., Hodel, M. R., Berland, K. M., Corbett, A. H. (2006). Nuclear Localization Signal Receptor Affinity Correlates with in Vivo Localization in Saccharomyces cerevisiae. J. Biol. Chem. 281: 23545-23556 [Abstract] [Full Text]
Butterfield-Gerson, K. L., Scheifele, L. Z., Ryan, E. P., Hopper, A. K., Parent, L. J. (2006). Importin-{beta} Family Members Mediate Alpharetrovirus Gag Nuclear Entry via Interactions with Matrix and Nucleocapsid. J. Virol. 80: 1798-1806 [Abstract] [Full Text]
Berger, A. C., Vanderford, T. H., Gernert, K. M., Nichols, J. W., Faundez, V., Corbett, A. H. (2005). Saccharomyces cerevisiae Npc2p Is a Functionally Conserved Homologue of the Human Niemann-Pick Disease Type C 2 Protein, hNPC2. Eukaryot Cell 4: 1851-1862 [Abstract] [Full Text]
Milgrom, E., West, R. W. Jr., Gao, C., Shen, W.-C. W. (2005). TFIID and Spt-Ada-Gcn5-Acetyltransferase Functions Probed by Genome-wide Synthetic Genetic Array Analysis Using a Saccharomyces cerevisiae taf9-ts Allele. Genetics 171: 959-973 [Abstract] [Full Text]
Lau, C. K., Giddings, T. H. Jr., Winey, M. (2004). A Novel Allele of Saccharomyces cerevisiae NDC1 Reveals a Potential Role for the Spindle Pole Body Component Ndc1p in Nuclear Pore Assembly. Eukaryot Cell 3: 447-458 [Abstract] [Full Text]
Tanaka, M., Nishi, M., Morimoto, M., Sugimoto, T., Kawata, M. (2003). Yellow Fluorescent Protein-Tagged and Cyan Fluorescent Protein-Tagged Imaging Analysis of Glucocorticoid Receptor and Importins in Single Living Cells. Endocrinology 144: 4070-4079 [Abstract] [Full Text]
Harreman, M. T., Hodel, M. R., Fanara, P., Hodel, A. E., Corbett, A. H. (2003). The Auto-inhibitory Function of Importin alpha Is Essential in Vivo. J. Biol. Chem. 278: 5854-5863 [Abstract] [Full Text]
Stade, K., Vogel, F., Schwienhorst, I., Meusser, B., Volkwein, C., Nentwig, B., Dohmen, R. J., Sommer, T. (2002). A Lack of SUMO Conjugation Affects cNLS-dependent Nuclear Protein Import in Yeast. J. Biol. Chem. 277: 49554-49561 [Abstract] [Full Text]
Schwoebel, E. D., Ho, T. H., Moore, M. S. (2002). The mechanism of inhibition of Ran-dependent nuclear transport by cellular ATP depletion. JCB 157: 963-974 [Abstract] [Full Text]
Mason, D. A., Fleming, R. J., Goldfarb, D. S. (2002). Drosophila melanogaster Importin {alpha}1 and {alpha}3 Can Replace Importin {alpha}2 During Spermatogenesis but Not Oogenesis. Genetics 161: 157-170 [Abstract] [Full Text]
Wang, H., Liu, D., Wang, Y., Qin, J., Elledge, S. J. (2001). Pds1 phosphorylation in response to DNA damage is essential for its DNA damage checkpoint function. Genes Dev. 15: 1361-1372 [Abstract] [Full Text]
Mosammaparast, N., Jackson, K. R., Guo, Y., Brame, C. J., Shabanowitz, J., Hunt, D. F., Pemberton, L. F. (2001). Nuclear Import of Histone H2a and H2b Is Mediated by a Network of Karyopherins. JCB 153: 251-262 [Abstract] [Full Text]
Künzler, M., Trueheart, J., Sette, C., Hurt, E., Thorner, J. (2001). Mutations in the YRB1 Gene Encoding Yeast Ran-Binding-Protein-1 That Impair Nucleocytoplasmic Transport and Suppress Yeast Mating Defects. Genetics 157: 1089-1105 [Abstract] [Full Text]
Stage-Zimmermann, T., Schmidt, U., Silver, P. A. (2000). Factors Affecting Nuclear Export of the 60S Ribosomal Subunit In Vivo. Mol. Biol. Cell 11: 3777-3789 [Abstract] [Full Text]
Fahrenkrog, B., Hübner, W., Mandinova, A., Panté, N., Keller, W., Aebi, U. (2000). The Yeast Nucleoporin Nup53p Specifically Interacts with Nic96p and Is Directly Involved in Nuclear Protein Import. Mol. Biol. Cell 11: 3885-3896 [Abstract] [Full Text]
Costa, P. J., Arndt, K. M. (2000). Synthetic Lethal Interactions Suggest a Role for the Saccharomyces cerevisiae Rtf1 Protein in Transcription Elongation. Genetics 156: 535-547 [Abstract] [Full Text]
Künzler, M., Gerstberger, T., Stutz, F., Bischoff, F. R., Hurt, E. (2000). Yeast Ran-Binding Protein 1 (Yrb1) Shuttles between the Nucleus and Cytoplasm and Is Exported from the Nucleus via a CRM1 (XPO1)-Dependent Pathway. Mol. Cell. Biol. 20: 4295-4308 [Abstract] [Full Text]
Vainberg, I. E., Dower, K., Rosbash, M. (2000). Nuclear Export of Heat Shock and Non-Heat-Shock mRNA Occurs via Similar Pathways. Mol. Cell. Biol. 20: 3996-4005 [Abstract] [Full Text]
Hood, J., Casolari, J., Silver, P. (2000). Nup2p is located on the nuclear side of the nuclear pore complex and coordinates Srp1p/importin-alpha export. J. Cell Sci. 113: 1471-1480 [Abstract]
Nanduri, J., Mitra, S., Andrei, C., Liu, Y., Yu, Y., Hitomi, M., Tartakoff, A. M. (1999). An Unexpected Link between the Secretory Path and the Organization of the Nucleus. J. Biol. Chem. 274: 33785-33789 [Abstract] [Full Text]
Booth, J. W., Belanger, K. D., Sannella, M. I., Davis, L. I. (1999). The Yeast Nucleoporin Nup2p Is Involved in Nuclear Export of Importin alpha /Srp1p. J. Biol. Chem. 274: 32360-32367 [Abstract] [Full Text]
Morehouse, H., Buratowski, R. M., Silver, P. A., Buratowski, S. (1999). The importin/karyopherin Kap114 mediates the nuclear import of TATA-binding protein. Proc. Natl. Acad. Sci. USA 96: 12542-12547 [Abstract] [Full Text]
Moy, T. I., Silver, P. A. (1999). Nuclear export of the small ribosomal subunit requires the Ran-GTPase cycle and certain nucleoporins. Genes Dev. 13: 2118-2133 [Abstract] [Full Text]
Hubner, S., Smith, H. M. S., Hu, W., Chan, C. K., Rihs, H.-P., Paschal, B. M., Raikhel, N. V., Jans, D. A. (1999). Plant Importin alpha Binds Nuclear Localization Sequences with High Affinity and Can Mediate Nuclear Import Independent of Importin beta. J. Biol. Chem. 274: 22610-22617 [Abstract] [Full Text]
Liu, Y., Guo, W., Tartakoff, P. Y., Tartakoff, A. M. (1999). A Crm1p-independent nuclear export path for the mRNA-associated protein, Npl3p/Mtr13p. Proc. Natl. Acad. Sci. USA 96: 6739-6744 [Abstract] [Full Text]
Siebel, C. W., Feng, L., Guthrie, C., Fu, X.-D. (1999). Conservation in budding yeast of a kinase specific for SR splicing factors. Proc. Natl. Acad. Sci. USA 96: 5440-5445 [Abstract] [Full Text]
Hieda, M., Tachibana, T., Yokoya, F., Kose, S., Imamoto, N., Yoneda, Y. (1999). A Monoclonal Antibody to the COOH-terminal Acidic Portion of Ran Inhibits Both the Recycling of Ran and Nuclear Protein Import in Living Cells. JCB 144: 645-655 [Abstract] [Full Text]
Hurt, E., Hannus, S., Schmelzl, B., Lau, D., Tollervey, D., Simos, G. (1999). A Novel In Vivo Assay Reveals Inhibition of Ribosomal Nuclear Export in Ran-Cycle and Nucleoporin Mutants. JCB 144: 389-401 [Abstract] [Full Text]
Seedorf, M., Damelin, M., Kahana, J., Taura, T., Silver, P. A. (1999). Interactions between a Nuclear Transporter and a Subset of Nuclear Pore Complex Proteins Depend on Ran GTPase. Mol. Cell. Biol. 19: 1547-1557 [Abstract] [Full Text]
Hood, J. K., Silver, P. A. (1998). Cse1p Is Required for Export of Srp1p/Importin-alpha from the Nucleus in Saccharomyces cerevisiae. J. Biol. Chem. 273: 35142-35146 [Abstract] [Full Text]
Solsbacher, J., Maurer, P., Bischoff, F. R., Schlenstedt, G. (1998). Cse1p Is Involved in Export of Yeast Importin alpha �from the Nucleus. Mol. Cell. Biol. 18: 6805-6815 [Abstract] [Full Text]
Taura, T., Krebber, H., Silver, P. A. (1998). A member of the Ran-binding protein family, Yrb2p, is involved in nuclear protein export. Proc. Natl. Acad. Sci. USA 95: 7427-7432 [Abstract] [Full Text]
Toone, W. M., Kuge, S., Samuels, M., Morgan, B. A., Toda, T., Jones, N. (1998). 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. 12: 1453-1463 [Abstract] [Full Text]
Truant, R., Fridell, R. A., Benson, R. E., Bogerd, H., Cullen, B. R. (1998). Identification and Functional Characterization of a Novel Nuclear Localization Signal Present in the Yeast Nab2 Poly(A)+ RNA Binding Protein. Mol. Cell. Biol. 18: 1449-1458 [Abstract] [Full Text]
Shen, E. C., Henry, M. F., Weiss, V. H., Valentini, S. R., Silver, P. A., Lee, M. S. (1998). Arginine methylation facilitates the nuclear export of hnRNP�proteins. Genes Dev. 12: 679-691 [Abstract] [Full Text]
Mahajan, R., Gerace, L., Melchior, F. (1998). Molecular Characterization of the SUMO-1 Modification of RanGAP1 and Its Role in Nuclear Envelope Association. JCB 140: 259-270 [Abstract] [Full Text]
Vodicka, M. A., Koepp, D. M., Silver, P. A., Emerman, M. (1998). HIV-1 Vpr interacts with the nuclear transport pathway to promote macrophage�infection. Genes Dev. 12: 175-185 [Abstract] [Full Text]
Pemberton, L. F., Rosenblum, J. S., Blobel, G. (1997). A Distinct and Parallel Pathway for the Nuclear Import of an mRNA-binding Protein. JCB 139: 1645-1653 [Abstract] [Full Text]
Taura, T., Schlenstedt, G., Silver, P. A. (1997). Yrb2p Is a Nuclear Protein That Interacts with Prp20p, a Yeast Rcc1 Homologue. J. Biol. Chem. 272: 31877-31884 [Abstract] [Full Text]
Kose, S., Imamoto, N., Tachibana, T., Shimamoto, T., Yoneda, Y. (1997). Ran-unassisted Nuclear Migration of a 97-kD Component of Nuclear Pore-targeting Complex. JCB 139: 841-849 [Abstract] [Full Text]
Boche, I., Fanning, E. (1997). Nucleocytoplasmic Recycling of the Nuclear Localization Signal Receptor {alpha} Subunit In Vivo Is Dependent on a Nuclear Export Signal, Energy, and RCC1. JCB 139: 313-325 [Abstract] [Full Text]
Pu, R. T., Dasso, M. (1997). The Balance of RanBP1 and RCC1 Is Critical for Nuclear Assembly and Nuclear Transport. Mol. Biol. Cell 8: 1955-1970 [Abstract] [Full Text]
Moroianu, J., Blobel, G., Radu, A. (1997). RanGTP-mediated nuclear export of karyopherin alpha �involves its interaction with the nucleoporin�Nup153. Proc. Natl. Acad. Sci. USA 94: 9699-9704 [Abstract] [Full Text]
Seedorf, M., Silver, P. A. (1997). Importin/karyopherin protein family members required for mRNA export from the�nucleus. Proc. Natl. Acad. Sci. USA 94: 8590-8595 [Abstract] [Full Text]
Floer, M., Blobel, G., Rexach, M. (1997). Disassembly of RanGTP-Karyopherin beta �Complex, an Intermediate in Nuclear Protein Import. J. Biol. Chem. 272: 19538-19546 [Abstract] [Full Text]
Gorlich, D., Dabrowski, M., Bischoff, F. R., Kutay, U., Bork, P., Hartmann, E., Prehn, S., Izaurralde, E. (1997). A Novel Class of RanGTP Binding Proteins. JCB 138: 65-80 [Abstract] [Full Text]
Iovine, M. K., Wente, S. R. (1997). A Nuclear Export Signal in Kap95p Is Required for Both Recycling the Import Factor and Interaction with the Nucleoporin GLFG Repeat Regions of Nup116p and Nup100p. JCB 137: 797-811 [Abstract] [Full Text]
Corbett, A. H., Silver, P. A. (1996). The NTF2 Gene Encodes an Essential, Highly Conserved Protein That Functions in Nuclear Transport in Vivo. J. Biol. Chem. 271: 18477-18484 [Abstract] [Full Text]
Quimby, B. B., Lamitina, T., L'Hernault, S. W., Corbett, A. H. (2000). The Mechanism of Ran Import into the Nucleus by Nuclear Transport Factor 2. J. Biol. Chem. 275: 28575-28582 [Abstract] [Full Text]