Systems analysis of Ran transport.
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.
Smith
Alicia E
AE
Center for Cell Signaling, Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, USA.
Slepchenko
Boris M
BM
Schaff
James C
JC
Loew
Leslie M
LM
Macara
Ian G
IG
D021581:Active Transport, Cell Nucleus; D000818:Animals; D018797:Cell Cycle Proteins; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003198:Computer Simulation; D006224:Cricetinae; D003593:Cytoplasm / Q000378:metabolism; D004058:Diffusion; D005453:Fluorescence; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D007700:Kinetics; D008433:Mathematics; D008954:Models, Biological; D009154:Mutation; D022022:Nuclear Pore / Q000378:metabolism*; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D013696:Temperature; D020931:ran GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
D018797:Cell Cycle Proteins; D020662:Guanine Nucleotide Exchange Factors; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; D011994:Recombinant Proteins; D006160:Guanosine Triphosphate; D020931:ran GTP-Binding Protein