Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 18 January 2002:
Vol. 295. no. 5554, pp. 488 - 491
DOI: 10.1126/science.1064732
Prev | Table of Contents | Next

Reports

Systems Analysis of Ran Transport

Alicia E. Smith,1 Boris M. Slepchenko,2 James C. Schaff,2 Leslie M. Loew,2 Ian G. Macara1*

The separate components of nucleocytoplasmic transport have been well characterized, including the key regulatory role of Ran, a guanine nucleotide triphosphatase. However, the overall system behavior in intact cells is difficult to analyze because the dynamics of these components are interdependent. We used a combined experimental and computational approach to study Ran transport in vivo. The resulting model provides the first quantitative picture of Ran flux between the nuclear and cytoplasmic compartments in eukaryotic cells. The model predicts that the Ran exchange factor RCC1, and not the flux capacity of the nuclear pore complex (NPC), is the crucial regulator of steady-state flux across the NPC. Moreover, it provides the first estimate of the total in vivo flux (520 molecules per NPC per second and predicts that the transport system is robust.

1 Center for Cell Signaling, Departments of Pharmacology and Microbiology, University of Virginia, Charlottesville, VA 22908, USA.
2 Center for Biomedical Imaging Technology, University of Connecticut Health Center, Farmington, CT 06030, USA.
*   To whom correspondence should be addressed. E-mail: igm9c{at}virginia.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Flexible Gates: Dynamic Topologies and Functions for FG Nucleoporins in Nucleocytoplasmic Transport.
L. J. Terry and S. R. Wente (2009)
Eukaryot. Cell 8, 1814-1827
   Abstract »    Full Text »    PDF »
The RanGTP gradient - a GPS for the mitotic spindle.
P. Kalab and R. Heald (2008)
J. Cell Sci. 121, 1577-1586
   Abstract »    Full Text »    PDF »
RANBP1 localizes a subset of mitotic regulatory factors on spindle microtubules and regulates chromosome segregation in human cells.
A. Tedeschi, M. Ciciarello, R. Mangiacasale, E. Roscioli, W. M. Rensen, and P. Lavia (2007)
J. Cell Sci. 120, 3748-3761
   Abstract »    Full Text »    PDF »
Reversibility in nucleocytoplasmic transport.
R. B. Kopito and M. Elbaum (2007)
PNAS 104, 12743-12748
   Abstract »    Full Text »    PDF »
Classical Nuclear Localization Signals: Definition, Function, and Interaction with Importin {alpha}.
A. Lange, R. E. Mills, C. J. Lange, M. Stewart, S. E. Devine, and A. H. Corbett (2007)
J. Biol. Chem. 282, 5101-5105
   Abstract »    Full Text »    PDF »
Calcium-Dependent Regulation of NEMO Nuclear Export in Response to Genotoxic Stimuli.
C. M. Berchtold, Z.-H. Wu, T. T. Huang, and S. Miyamoto (2007)
Mol. Cell. Biol. 27, 497-509
   Abstract »    Full Text »    PDF »
Simple kinetic relationships and nonspecific competition govern nuclear import rates in vivo.
B. L. Timney, J. Tetenbaum-Novatt, D. S. Agate, R. Williams, W. Zhang, B. T. Chait, and M. P. Rout (2006)
J. Cell Biol. 175, 579-593
   Abstract »    Full Text »    PDF »
Nuclear Localization Signal Receptor Affinity Correlates with in Vivo Localization in Saccharomyces cerevisiae.
A. E. Hodel, M. T. Harreman, K. F. Pulliam, M. E. Harben, J. S. Holmes, M. R. Hodel, K. M. Berland, and A. H. Corbett (2006)
J. Biol. Chem. 281, 23545-23556
   Abstract »    Full Text »    PDF »
Systems biology in the cell nucleus.
S. Gorski and T. Misteli (2005)
J. Cell Sci. 118, 4083-4092
   Abstract »    Full Text »    PDF »
A systems analysis of importin-{alpha}-{beta} mediated nuclear protein import.
G. Riddick and I. G. Macara (2005)
J. Cell Biol. 168, 1027-1038
   Abstract »    Full Text »    PDF »
Kinetic and Molecular Analysis of Nuclear Export Factor CRM1 Association with Its Cargo In Vivo.
D. Daelemans, S. V. Costes, S. Lockett, and G. N. Pavlakis (2005)
Mol. Cell. Biol. 25, 728-739
   Abstract »    Full Text »    PDF »
Importin {beta} is transported to spindle poles during mitosis and regulates Ran-dependent spindle assembly factors in mammalian cells.
M. Ciciarello, R. Mangiacasale, C. Thibier, G. Guarguaglini, E. Marchetti, B. Di Fiore, and P. Lavia (2004)
J. Cell Sci. 117, 6511-6522
   Abstract »    Full Text »    PDF »
A systems view of mRNP biology.
H. Hieronymus and P. A. Silver (2004)
Genes & Dev. 18, 2845-2860
   Abstract »    Full Text »    PDF »
Nuclear Export of the Yeast mRNA-binding Protein Nab2 Is Linked to a Direct Interaction with Gfd1 and to Gle1 Function.
M. Suntharalingam, A. R. Alcazar-Roman, and S. R. Wente (2004)
J. Biol. Chem. 279, 35384-35391
   Abstract »    Full Text »    PDF »
Minihelix-containing RNAs Mediate Exportin-5-dependent Nuclear Export of the Double-stranded RNA-binding Protein ILF3.
C. Gwizdek, B. Ossareh-Nazari, A. M. Brownawell, S. Evers, I. G. Macara, and C. Dargemont (2004)
J. Biol. Chem. 279, 884-891
   Abstract »    Full Text »    PDF »
Biochemical Characterization of the Ran-RanBP1-RanGAP System: Are RanBP Proteins and the Acidic Tail of RanGAP Required for the Ran-RanGAP GTPase Reaction?.
M. J. Seewald, A. Kraemer, M. Farkasovsky, C. Korner, A. Wittinghofer, and I. R. Vetter (2003)
Mol. Cell. Biol. 23, 8124-8136
   Abstract »    Full Text »    PDF »
Physical and Functional Modularity of the Protein Network in Yeast.
T. Wilhelm, H.-P. Nasheuer, and S. Huang (2003)
Mol. Cell. Proteomics 2, 292-298
   Abstract »    Full Text »    PDF »
E1A Deregulates the Centrosome Cycle in a Ran GTPase-dependent Manner.
A. De Luca, R. Mangiacasale, A. Severino, L. Malquori, A. Baldi, A. Palena, A. M. Mileo, P. Lavia, and M. G. Paggi (2003)
Cancer Res. 63, 1430-1437
   Abstract »    Full Text »    PDF »
Structural Adaptation of the Nuclear Pore Complex in Stem Cell-Derived Cardiomyocytes.
C. Perez-Terzic, A. Behfar, A. Mery, J. M.A. van Deursen, A. Terzic, and M. Puceat (2003)
Circ. Res. 92, 444-452
   Abstract »    Full Text »    PDF »
Exportin-5 Mediates Nuclear Export of Minihelix-containing RNAs.
C. Gwizdek, B. Ossareh-Nazari, A. M. Brownawell, A. Doglio, E. Bertrand, I. G. Macara, and C. Dargemont (2003)
J. Biol. Chem. 278, 5505-5508
   Abstract »    Full Text »    PDF »
The Ran GTPase System in Fission Yeast Affects Microtubules and Cytokinesis in Cells That Are Competent for Nucleocytoplasmic Protein Transport.
S. S. Salus, J. Demeter, and S. Sazer (2002)
Mol. Cell. Biol. 22, 8491-8505
   Abstract »    Full Text »    PDF »
Fluorescence Resonance Energy Transfer Biosensors That Detect Ran Conformational Changes and a Ran{middle dot}GDP-Importin-beta -RanBP1 Complex in Vitro and in Intact Cells.
K. Plafker and I. G. Macara (2002)
J. Biol. Chem. 277, 30121-30127
   Abstract »    Full Text »    PDF »
SMN, the spinal muscular atrophy protein, forms a pre-import snRNP complex with snurportin1 and importin {beta}.
U. Narayanan, J. K. Ospina, M. R. Frey, M. D. Hebert, and A. G. Matera (2002)
Hum. Mol. Genet. 11, 1785-1795
   Abstract »    Full Text »    PDF »
Ran-binding Protein 3 Links Crm1 to the Ran Guanine Nucleotide Exchange Factor.
M. E. Nemergut, M. E. Lindsay, A. M. Brownawell, and I. G. Macara (2002)
J. Biol. Chem. 277, 17385-17388
   Abstract »    Full Text »    PDF »
What makes Ran run?.
W. A. Wells (2002)
J. Cell Biol. 156, 412-413
   Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)