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. 2010 Dec 21;6:446. doi: 10.1038/msb.2010.102

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Copyright © 2010, EMBO and Macmillan Publishers Limited

This is an open-access article distributed under the terms of the Creative Commons Attribution Noncommercial Share Alike 3.0 Unported License, which allows readers to alter, transform, or build upon the article and then distribute the resulting work under the same or similar license to this one. The work must be attributed back to the original author and commercial use is not permitted without specific permission.

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Active export of importins rather than active import of the importin–NR complex is advantageous for enhancing the transcriptional response. Three alternative network designs are depicted: (A) Passive facilitated diffusion (reversible pore) of NR across the nuclear membrane; (B) Active nuclear import of importin–NR complex; (C) Active export of importins from the nucleus. (D) Steady-state transcriptional response (ratio ReNrL/Re_total) as function of the total concentration of importins (A–C; note the logarithmic importin concentration axis). The transcriptional response represents the fraction of REs complexed to the NRL. (E) Sequestration (defined as the ratio NrL_totalImp_total/NrL_total) as function of the total concentration of importins (A–C; note the logarithmic importin concentration axis). Rate equations and kinetic parameters are given in Supplementary Table 7. Supplementary Figure 5S shows simulation results for all species. As compared with Figure 2, the model was simplified by only considering the liganded fraction of the NR (fixed at the level equal to the concentration of NRL in design 4 of Figure 2; in reality, for the case of active transport, the fraction of NRL and consequently the maximal transcriptional response may be larger due to elevated concentration of ligand in the nucleus, in accordance with the design principles discussed above). NrL, liganded NR (e.g., GR); Imp, importins; NrLImp, liganded NR bound with importins; Re, RE for NR on DNA; ReNrL, RE on DNA bound with activated NR; NPC, nuclear pore complex. The model is available in JWS Online and can be simulated in its web browser: http://jjj.biochem.sun.ac.za; http://jjj.bio.vu.nl; http://jjj.mib.ac.uk (Snoep and Olivier, 2002; Olivier and Snoep, 2004). The model can be found via ‘author search’, ‘kolodkin7’. The model can be also accessed directly via: http://jjj.bio.vu.nl/webMathematica/Examples/run.jsp?modelName=kolodkin7 or at any of the other servers listed above. Please note that values of parameters for nuclear import/export rates are set for reversible transport. Simulations of receptor (importin) pump require parameter values from Supplementary Table 7.