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HFSP J
2009 Jan 01;32:130-41. doi: 10.2976/1.3080807.
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Nucleocytoplasmic transport: a thermodynamic mechanism.
Kopito RB, Elbaum M.
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The nuclear pore supports molecular communication between cytoplasm and nucleus in eukaryotic cells. Selective transport of proteins is mediated by soluble receptors, whose regulation by the small GTPase Ran leads to cargo accumulation in, or depletion from, the nucleus, i.e., nuclear import or nuclear export. We consider the operation of this transport system by a combined analytical and experimental approach. Provocative predictions of a simple model were tested using cell-free nuclei reconstituted in Xenopus egg extract, a system well suited to quantitative studies. We found that accumulation capacity is limited, so that introduction of one import cargo leads to egress of another. Clearly, the pore per se does not determine transport directionality. Moreover, different cargo reach a similar ratio of nuclear to cytoplasmic concentration in steady-state. The model shows that this ratio should in fact be independent of the receptor-cargo affinity, though kinetics may be strongly influenced. Numerical conservation of the system components highlights a conflict between the observations and the popular concept of transport cycles. We suggest that chemical partitioning provides a framework to understand the capacity to generate concentration gradients by equilibration of the receptor-cargo intermediary.
Adam,
Nuclear protein import in permeabilized mammalian cells requires soluble cytoplasmic factors.
1990, Pubmed,
Xenbase
Adam,
Nuclear protein import in permeabilized mammalian cells requires soluble cytoplasmic factors.
1990,
Pubmed
,
Xenbase Akey,
Architecture of the Xenopus nuclear pore complex revealed by three-dimensional cryo-electron microscopy.
1993,
Pubmed
,
Xenbase Alber,
The molecular architecture of the nuclear pore complex.
2007,
Pubmed Bapteste,
The two tempos of nuclear pore complex evolution: highly adapting proteins in an ancient frozen structure.
2005,
Pubmed Beck,
Snapshots of nuclear pore complexes in action captured by cryo-electron tomography.
2007,
Pubmed Becskei,
The strategy for coupling the RanGTP gradient to nuclear protein export.
2003,
Pubmed
,
Xenbase Ben-Efraim,
Gradient of increasing affinity of importin beta for nucleoporins along the pathway of nuclear import.
2001,
Pubmed Bickel,
The nuclear pore complex mystery and anomalous diffusion in reversible gels.
2002,
Pubmed Caspi,
Synthetic mimic of selective transport through the nuclear pore complex.
2008,
Pubmed Catimel,
Biophysical characterization of interactions involving importin-alpha during nuclear import.
2001,
Pubmed Cingolani,
Molecular basis for the recognition of a nonclassical nuclear localization signal by importin beta.
2002,
Pubmed Coppey,
Modeling the bicoid gradient: diffusion and reversible nuclear trapping of a stable protein.
2007,
Pubmed Costa,
Dynamic regulation of ERK2 nuclear translocation and mobility in living cells.
2006,
Pubmed Cronshaw,
Proteomic analysis of the mammalian nuclear pore complex.
2002,
Pubmed Dange,
Autonomy and robustness of translocation through the nuclear pore complex: a single-molecule study.
2008,
Pubmed Denning,
Rapid evolution exposes the boundaries of domain structure and function in natively unfolded FG nucleoporins.
2007,
Pubmed Devos,
Components of coated vesicles and nuclear pore complexes share a common molecular architecture.
2004,
Pubmed Fanara,
Quantitative analysis of nuclear localization signal (NLS)-importin alpha interaction through fluorescence depolarization. Evidence for auto-inhibitory regulation of NLS binding.
2000,
Pubmed Fornerod,
CRM1 is an export receptor for leucine-rich nuclear export signals.
1997,
Pubmed
,
Xenbase Fradin,
Fluorescence correlation spectroscopy close to a fluctuating membrane.
2003,
Pubmed Fradin,
Dissociation of nuclear import cargo complexes by the protein Ran: a fluorescence correlation spectroscopy study.
2005,
Pubmed Frey,
A saturated FG-repeat hydrogel can reproduce the permeability properties of nuclear pore complexes.
2007,
Pubmed Fukuda,
CRM1 is responsible for intracellular transport mediated by the nuclear export signal.
1997,
Pubmed
,
Xenbase Görlich,
Characterization of Ran-driven cargo transport and the RanGTPase system by kinetic measurements and computer simulation.
2003,
Pubmed Görlich,
Transport between the cell nucleus and the cytoplasm.
1999,
Pubmed Gorski,
The road much traveled: trafficking in the cell nucleus.
2006,
Pubmed Gregor,
Stability and nuclear dynamics of the bicoid morphogen gradient.
2007,
Pubmed Grünwald,
Probing intranuclear environments at the single-molecule level.
2008,
Pubmed Harreman,
The auto-inhibitory function of importin alpha is essential in vivo.
2003,
Pubmed Henderson,
3-D ultrastructure of O. tauri: electron cryotomography of an entire eukaryotic cell.
2007,
Pubmed Hinshaw,
Architecture and design of the nuclear pore complex.
1992,
Pubmed
,
Xenbase Hodel,
Nuclear localization signal receptor affinity correlates with in vivo localization in Saccharomyces cerevisiae.
2006,
Pubmed Hu,
Kinetic properties of nuclear transport conferred by the retinoblastoma (Rb) NLS.
2005,
Pubmed
,
Xenbase Hübner,
Plant importin alpha binds nuclear localization sequences with high affinity and can mediate nuclear import independent of importin beta.
1999,
Pubmed Jovanovic-Talisman,
Artificial nanopores that mimic the transport selectivity of the nuclear pore complex.
2009,
Pubmed Kalab,
Visualization of a Ran-GTP gradient in interphase and mitotic Xenopus egg extracts.
2002,
Pubmed
,
Xenbase Kalderon,
A short amino acid sequence able to specify nuclear location.
1984,
Pubmed Kapon,
A possible mechanism for self-coordination of bidirectional traffic across nuclear pores.
2008,
Pubmed Kobe,
Autoinhibition by an internal nuclear localization signal revealed by the crystal structure of mammalian importin alpha.
1999,
Pubmed Köhler,
Evidence for distinct substrate specificities of importin alpha family members in nuclear protein import.
1999,
Pubmed
,
Xenbase Kopito,
Reversibility in nucleocytoplasmic transport.
2007,
Pubmed
,
Xenbase Kose,
beta-subunit of nuclear pore-targeting complex (importin-beta) can be exported from the nucleus in a Ran-independent manner.
1999,
Pubmed Kotera,
Importin alpha transports CaMKIV to the nucleus without utilizing importin beta.
2005,
Pubmed Kubitscheck,
Nuclear transport of single molecules: dwell times at the nuclear pore complex.
2005,
Pubmed Kustanovich,
Metastable network model of protein transport through nuclear pores.
2004,
Pubmed Lam,
Importin beta recognizes parathyroid hormone-related protein with high affinity and mediates its nuclear import in the absence of importin alpha.
1999,
Pubmed Lee,
Rules for nuclear localization sequence recognition by karyopherin beta 2.
2006,
Pubmed Lee,
The structure of importin-beta bound to SREBP-2: nuclear import of a transcription factor.
2003,
Pubmed Lohka,
Formation in vitro of sperm pronuclei and mitotic chromosomes induced by amphibian ooplasmic components.
1983,
Pubmed
,
Xenbase Lyman,
Influence of cargo size on Ran and energy requirements for nuclear protein import.
2002,
Pubmed Macara,
Transport into and out of the nucleus.
2001,
Pubmed Mans,
Comparative genomics, evolution and origins of the nuclear envelope and nuclear pore complex.
2004,
Pubmed Melcák,
Structure of Nup58/45 suggests flexible nuclear pore diameter by intermolecular sliding.
2007,
Pubmed Michael,
Nucleocytoplasmic shuttling signals: two for the price of one.
2000,
Pubmed Miyamoto,
Importin alpha can migrate into the nucleus in an importin beta- and Ran-independent manner.
2002,
Pubmed Nachury,
The direction of transport through the nuclear pore can be inverted.
1999,
Pubmed Naim,
Passive and facilitated transport in nuclear pore complexes is largely uncoupled.
2007,
Pubmed Nakielny,
Nup153 is an M9-containing mobile nucleoporin with a novel Ran-binding domain.
1999,
Pubmed Newmeyer,
In vitro transport of a fluorescent nuclear protein and exclusion of non-nuclear proteins.
1986,
Pubmed
,
Xenbase Ossareh-Nazari,
Evidence for a role of CRM1 in signal-mediated nuclear protein export.
1997,
Pubmed Pederson,
Diffusional protein transport within the nucleus: a message in the medium.
2000,
Pubmed Pemberton,
Mechanisms of receptor-mediated nuclear import and nuclear export.
2005,
Pubmed Peters,
Translocation through the nuclear pore complex: selectivity and speed by reduction-of-dimensionality.
2005,
Pubmed Phair,
High mobility of proteins in the mammalian cell nucleus.
2000,
Pubmed Pollard,
A novel receptor-mediated nuclear protein import pathway.
1996,
Pubmed Pyhtila,
A gradient of affinity for the karyopherin Kap95p along the yeast nuclear pore complex.
2003,
Pubmed Ribbeck,
The permeability barrier of nuclear pore complexes appears to operate via hydrophobic exclusion.
2002,
Pubmed Ribbeck,
NTF2 mediates nuclear import of Ran.
1998,
Pubmed Riddick,
The adapter importin-alpha provides flexible control of nuclear import at the expense of efficiency.
2007,
Pubmed Riddick,
A systems analysis of importin-{alpha}-{beta} mediated nuclear protein import.
2005,
Pubmed Rihs,
The rate of nuclear cytoplasmic protein transport is determined by the casein kinase II site flanking the nuclear localization sequence of the SV40 T-antigen.
1991,
Pubmed Robbins,
Two interdependent basic domains in nucleoplasmin nuclear targeting sequence: identification of a class of bipartite nuclear targeting sequence.
1991,
Pubmed
,
Xenbase Rout,
The yeast nuclear pore complex: composition, architecture, and transport mechanism.
2000,
Pubmed Salman,
Kinetics and mechanism of DNA uptake into the cell nucleus.
2001,
Pubmed
,
Xenbase Schmidt-Zachmann,
Nuclear export of proteins: the role of nuclear retention.
1993,
Pubmed
,
Xenbase Schwartz,
Modularity within the architecture of the nuclear pore complex.
2005,
Pubmed Shah,
Separate nuclear import pathways converge on the nucleoporin Nup153 and can be dissected with dominant-negative inhibitors.
,
Pubmed
,
Xenbase Smith,
Nuclear import of Ran is mediated by the transport factor NTF2.
,
Pubmed Stade,
Exportin 1 (Crm1p) is an essential nuclear export factor.
1997,
Pubmed Steggerda,
Monoclonal antibodies to NTF2 inhibit nuclear protein import by preventing nuclear translocation of the GTPase Ran.
2000,
Pubmed Stein,
Kinetics of transport: analyzing, testing, and characterizing models using kinetic approaches.
1989,
Pubmed Stewart,
Molecular mechanism of the nuclear protein import cycle.
2007,
Pubmed Stoffler,
The nuclear pore complex: from molecular architecture to functional dynamics.
1999,
Pubmed Strawn,
Minimal nuclear pore complexes define FG repeat domains essential for transport.
2004,
Pubmed Timney,
Simple kinetic relationships and nonspecific competition govern nuclear import rates in vivo.
2006,
Pubmed Tokunaga,
Highly inclined thin illumination enables clear single-molecule imaging in cells.
2008,
Pubmed Wen,
Identification of a signal for rapid export of proteins from the nucleus.
1995,
Pubmed Yang,
Three-dimensional architecture of the isolated yeast nuclear pore complex: functional and evolutionary implications.
1998,
Pubmed Yang,
Nuclear import time and transport efficiency depend on importin beta concentration.
2006,
Pubmed Yang,
Imaging of single-molecule translocation through nuclear pore complexes.
2004,
Pubmed Zeitler,
The FG-repeat asymmetry of the nuclear pore complex is dispensable for bulk nucleocytoplasmic transport in vivo.
2004,
Pubmed Zilman,
Efficiency, selectivity, and robustness of nucleocytoplasmic transport.
2007,
Pubmed
