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| Subject Categories: Membranes & Transport | Genomic & Computational Biology |
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| The EMBO Journal
(2003) 22, 1088–1100, doi:10.1093/emboj/cdg113 |
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| Characterization of Ran-driven cargo transport and the RanGTPase system by kinetic measurements and computer simulation |
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| Dirk Görlich2, Michael J. Seewald1 and Katharina Ribbeck3 |
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1 ZMBH, INF 282, 69120 Heidelberg, Germany 2 MPI für Molekulare Physiologie, Otto-Hahn-Str. 11, 44227 Dortmund, Germany 3 Present address: EMBL, Meyerhofstra  e 1, Heidelberg, GermanyTo whom correspondence should be addressed Dirk Görlich, dg@zmbh.uni-heidelberg.de Received 11 October 2002; Revised 9 January 2003; Accepted 14 January 2003. |
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| Abstract |
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Here, we analyse the RanGTPase system and its coupling to receptor-mediated nuclear transport. Our simulations predict nuclear RanGTP levels in HeLa cells to be very sensitive towards the cellular energy charge and to exceed the cytoplasmic concentration  1000-fold. The steepness of the RanGTP gradient appears limited by both the cytoplasmic RanGAP concentration and the imperfect retention of nuclear RanGTP by nuclear pore complexes (NPCs), but not by the nucleotide exchange activity of RCC1. Neither RanBP1 nor the NPC localization of RanGAP has a significant direct impact on the RanGTP gradient. NTF2-mediated import of Ran appears to be the bottleneck for maximal capacity of Ran-driven nuclear transport. We show that unidirectional nuclear transport can be faithfully simulated without the assumption of a vectorial NPC passage; transport receptors only need to reversibly cross NPCs and switch their affinity for cargo in response to the RanGTP gradient. A significant RanGTP gradient after nuclear envelope (NE) breakdown can apparently exist only in large cytoplasm. This indicates that RanGTP gradients can provide positional information for mitotic spindle and NE assembly in early embryonic cells, but hardly any in small somatic cells. |
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| Keywords: importin, kinetics, nuclear transport, translocation |
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