The molecular structure of the yeast nuclear pore complex npc and the translocation of model particles have been studied with a molecular theory that accounts for the geometry of the pore and the sequence and anchoring position of the unfolded domains of the nucleoporin proteins the fgnups, which control selective transport through the pore. Force triggers yap nuclear entry by regulating transport across nuclear pores alberto eloseguiartola,1, ion andreu,2,3 amy e. After translocation through the npc, rangtp displaces the cargo from the ntr, resulting in nuclear cargo. The yeast nuclear pore complex and transport through it. Energetics of transport through the nuclear pore complex. The nuclear pore complex is immense by molecular standards. While transport factors such as ran and ntf2 show only transient interaction with the pores, a number of soluble. Subdiffusion as a model of transport through the nuclear pore complex. The npc provides two types of nucleocytoplasmic transport. Precisely how nuclear pore complexes regulate macromolecular and ionic traffic remains unknown, but recent advances in the identification. This lecture on nuclear transport explains about nuclear pore complex structure and role of nuclear pore complex to transport proteins and genetic material in and out of nucleus. The nuclear pore complex and nuclear transport ncbi.
Brenner1, katharina ribbeck2 1school of engineering and applied sciences, harvard university, cambridge, massachusetts, united states of america, 2fas center for systems biology, harvard. Artificial nanopores that mimic the transport selectivity. The nuclear pore complex and nuclear transport susan r. Apr 14, 2015 the nuclear pore complex npc is an essential gateway between the cell nucleus and the cytoplasm. Recently, it was shown that transport of receptorcargo complexes across the. Covalently attaching nuclear pore proteins to solidstate nanopores forms a complex that can selectively transport certain proteins, similar to the nuclear pore complex. Beedle,4,5 ainhoa lezamiz,4,5 marina uroz,1 anita j. Singlemolecule transport across an individual biomimetic. Here, we show that force applied to the nucleus directly drives yap nuclear translocation by decreasing the mechanical restriction of nuclear pores to molecular transport. Transport routes through the nuclear pore complex sciencedirect. It also plays an important part in transcriptional regulation, signal transduction, cell growth, and the cell cycle strambiodecastillia et al.
The active transport mechanism of large macromolecules is driven by soluble nuclear transport factors ntf which mostly belong to the karyopherin family kap. Small molecules through the large pore of this multiprotein complex. Subdiffusion as a model of transport through the nuclear pore. Model of nuclear pore complex transport selectivity youtube. The molecular mechanism of translocation through the nuclear. Various models predict how cargos move through the channel. Yap is a mechanosensitive transcriptional activator with a critical role in cancer, regeneration, and organ size control. Kinetics of transport through the nuclear pore complex. Transportrelated structures and processes of the nuclear.
Probing the disordered domain of the nuclear pore complex et al. Some proteins form relatively permanent associations with the core structure, and so are termed nuclear pore complex components or nucleoporins nups. Ribbeck and gorlich suggested that the transport channel located in the center of the pore complex is occupied by a meshwork of fg repeat nucleoporins that functions as a semiliquid phase into which receptorcargo complexes, containing fgbinding sites, could partition and thereby translocate through the pores ribbeck and gorlich, 2001. Slideandexchange mechanism for rapid and selective transport through the nuclear pore complex.
Long unfolded linkers facilitate membrane protein import. Here, we show that the direction of transport through the npc can be inverted in the presence of high concentrations of cytoplasmic rangtp. Once inside the nucleus, interaction with rangtp causes a conformational change in the importin that causes it to dissociate from its cargo. Schwartz abstract nuclear pore complexes npcs are indispensable for cell function and are at the center of several human diseases. The molecular mechanism of transport of macromolecules. University of groningen coarsegrained molecular dynamics.
The transport mechanism relies on recognition of molecular cargos by receptor proteins, and on specific interaction between the receptors and the pores. Nuclear trafficking involves a complex series of interactions between cargo, soluble transport factors carriers and nuclear pore proteins nucleoporins that are orchestrated by the ras. A nuclear pore is a part of a large complex of proteins, known as a nuclear pore complex that spans the nuclear envelope, which is the double membrane surrounding the eukaryotic cell nucleus. Pdf the nuclear pore complex, nuclear transport, and. Nucleocytoplasmic transport affects the subcellular localization of a large proportion of cellular proteins. Energetics of transport through the nuclear pore complex plos. However, only eight plant nucleoporins have been identified, and little information is available about the complete molecular structure of plant npcs. It is generally assumed that both modes of transport occur through a single diffusion channel located within the central pore of the nuclear pore complex.
Nuclear pore complexes actively transport macromolecules between the nucleus and cytoplasm. Rout institute for systems biology and seattle biomedical research institute, seattle, washington 98109, and the laboratory of cellular and structural biology, the rockefeller university, new york, new york 10021. There are approximately 1,000 nuclear pore complexes npcs in the nuclear envelope of a vertebrate cell, but it varies depending on cell type and the stage in the life cycle. Nanoscale mechanism of molecular transport through the. The structure of the nuclear pore complex an update. Intrinsically disordered fgnups line the npc lumen and form a selective barrier, where transport of most proteins is inhibited whereas specific transporter proteins freely pass. The density of export receptors that must bind an mrna to ensure export, as well as how receptor distribution affects transport dynamics. Molecular transport across the nuclear envelope in eukaryotic cells is solely controlled by the nuclear pore complex npc. The nuclear pore complex npc facilitates nucleocytoplasmic transport, a crucial process for various cellular activities.
We found that at least a 120residuelong intrinsically disordered linker was required for the import of membrane. How nuclear membrane proteins cross through the npc to reach the inner membrane is presently unclear. Trafficking of macromolecules between nuclear and cytoplasmic compartments takes place through the nuclear pore complexes npcs of the nuclear envelope. Model of nuclear pore complex transport selectivity. Importin proteins bind their cargo in the cytoplasm, after which they are able to interact with the nuclear pore complex and pass through its channel.
The nuclear pore complex npc, perhaps the largest protein complex in the cell, is responsible for the protected exchange of components between the nucleus and cytoplasm and for preventing the transport of material not destined to cross the nuclear envelope. The npc comprises 30 nucleoporins and is well characterized in vertebrates and yeast. The npc is embodied in the nuclear envelope membranes and provides bidirectional pathways for passive transport of small molecules and active facilitated transport of larger molecules 14. Transport across the nuclear envelope is regulated by nuclear pore complexes npcs. Small molecules transport through the nuclear pore complex. Introduction understanding the chemical mechanism of molecular transport through the nuclear pore complex npc is required urgently in many research fields. Pdf the structure of the nuclear pore complex researchgate. Overall structure and molecular composition of the nuclear. Identification and characterization of nuclear pore complex. The nuclear pore complex structure and function at a glance greg kabachinski and thomas u. Abstract in eukaryotic cells, transport of molecules between the nucleus and the cytoplasm is facilitated by highly selective and efficient. Structure of the nuclear transport complex karyopherinbeta2ran x gppnhp. It generates an essential macromolecular separation between the nucleus and cytoplasm. Transportin carries the protein through a nuclear pore and into the nucleus.
The direction of transport through the nuclear pore can be inverted. Precisely how nuclear pore complexes regulate macromolecular and ionic traffic remains unknown, but recent advances in the identification and characterization of components of the complex by proteomics and genomics have provided new insights. Synthetic mimic of selective transport through the nuclear. Nuclear pore complexes npcs are the sole gateways that facilitate this macromolecular exchange across the nuclear envelope with the help of soluble transport.
Nuclear pore complex an overview sciencedirect topics. Kechagia,1 palma ricolastres,4,5 anabellise le roux,1 catherine m. Nanoscale electrostatic gating of molecular transport through. Asymmetric nups asymmetric nups formed by nuclear basket nups and cytoplasmic. Video imaging by highspeed atomic force microscopy captures a nuclear pore complex at. The nuclear envelope has many nuclear pores termed nuclear pore complex. An import complex consisting of an nlsbearing cargo and a nuclear transport receptor ntr is formed in the cytoplasm. This exchange requires a dedicated transport system. The yeast nuclear pore complex and transport through it john d.
We present a chemical mimic of this receptormediated. Nuclear pore complexes, the conduits for information exchange between the nucleus and cytoplasm, appear broadly similar in eukaryotes from yeast to human. Studded throughout the ne are portals called nuclear pore complexes. The nuclear pore complex structure and function at a glance. Rangtp is predominantly located in the nucleus and has been shown to regulate cargo binding and release of import and export receptors in their respective target compartments. Nuclear import and export through nuclear pore complexes. Rout laboratory of cellular and structural biology, the rockefeller university, new york, new york 10065 correspondence.
Here we present a singleparticle cryoelectron microscopy cryoem structure of the cr from xenopus laevis npc at average resolutions of 5. Active nuclear import of soluble cargo involves tra nsport factors that shuttle cargo through the nuclear pore complex npc by binding to phenylalaninegly cine fg domains. Jun 19, 2011 covalently attaching nuclear pore proteins to solidstate nanopores forms a complex that can selectively transport certain proteins, similar to the nuclear pore complex. The transport of molecules and macromolecules across the nuclear membrane occurs through the nu clear pore complexes npcs. There is emerging evidence that nuclear transport is a result of interactions between the phenylalanine rings of the fgrepeats and hydrophobic residues on the surface of the receptor fahrenkrog and aebi 2003. It has been shown that the interaction between intrinsically disordered proteins that line the central channel of. Slideandexchange mechanism for rapid and selective. Other proteins associate transiently with the npc, either constantly cycling on and off or attaching only at particular times in the cells life cycle. In addition to the wellcharacterized gtpdependent nuclear transport observed in permeabilized cells, we detected a mode of nuclear transport that was gtpindependent at elevated cytoplasmic calcium concentrations. There are approximately 1,000 nuclear pore complexes npcs in the nuclear envelope of a vertebrate cell, but it varies depending on cell type and the.
Recombinant calmodulin restored atpdependent nuclear transport in the. Small molecules and ions are passively transported through the. Active nuclear import of soluble cargo involves transport factors that shuttle cargo through the nuclear pore complex npc by binding to phenylalanineglycine fg domains. Nuclear pores are large complex structures in the nuclear envelope doublemembrane that regulate movement of macromolecules proteins and nucleic acids in and out of the nucleus. The nuclear pore complex npc, a large transporter spanning the nuclear envelope and thus interfacing genetic information with protein synthesis, displays a puzzling functional duality. Pdf molecular transport across the nuclear envelope in eukaryotic cells is solely controlled by the nuclear pore complex npc.
The nuclear pore complex npc serves as the sole bidirectional gateway of macromolecules in and out of the nucleus. Pdf energetics of transport through the nuclear pore complex. The mechanism of nucleocytoplasmic transport through the. A passively impermeable macromolecule tagged with a signal peptide is chaperoned through the nanopore by nuclear transport. The nuclear pore complex npc is the sole gateway between the nucleus and the cytoplasm of interphase eukaryotic cells, and it mediates all trafficking between these 2 cellular compartments. Other proteins associate transiently with the npc, either constantly cycling on and off or attaching only at particular times in. Nup153 is an m9containing mobile nucleoporin with a novel ranbinding domain.
Molecular traffic between nucleus and cytoplasm is routed through nuclear pore complexes npcs embedded in the nuclear envelope 3. Nuclear transport an overview sciencedirect topics. Neutral molecules containing neither nuclear transport signals nor binding to phenylalanine glycine fg motifs of npc proteins nucleoporins seem to permeate the npc by diffusing through a tube of 810 nm. The npc allows for passive diffusion of small molecules including sugars, ions, and water, while simultaneously imposing sizedependent exclusion of macromolecules without nuclear transport factor tf binding. The nuclear pore complex is a large protein channel present universally in eukaryotic cells. Structural studies have now provided atomicresolution crystal structures of most nucleoporins. The nuclear pore complex npc, residing in the nuclear envelope ne, is the main mediator of transport between the nucleus and the cytoplasm in all eukaryotic cells christie et al. Oct 19, 2012 this lecture on nuclear transport explains about nuclear pore complex structure and role of nuclear pore complex to transport proteins and genetic material in and out of nucleus. It is made up of multiple copies of some 50 100 different proteins. As they must shuttle back to the nucleus to fulfill this function it is possible that they also mediate protein import. Jan 15, 20 the nuclear pore complex npc is the proteinaceous nanopore that solely mediates molecular transport across the nuclear envelope between the nucleus and cytoplasm of a eukaryotic cell. Structure of the cytoplasmic ring of the xenopus laevis.
During import or export the appropriate ntf binds to cargo with nuclear import or export signals, upon which the. Subdiffusion as a model of transport through the nuclear. Much is understood about the factors that shuttle and control the movement of cargos through the npc, but less has been resolved about the translocation process itself. One can envision the npc as being comprised of layers of interacting proteins, starting with the core structure, moving outwards through its peripheral. The mechanism of nucleocytoplasmic transport through the nuclear pore complex j. Pdf the yeast nuclear pore complex and transport through it. Collectively, fgrich regions build the diffusion barrier of the npc. The nuclear pore complex npc regulates macromolecular transport between the nucleus and the cytoplasm in all eukaryotic cells 1, 2. The nuclear pore complex as a flexible and dynamic gate. Identification and characterization of nuclear pore. The nuclear pore complex and nuclear transport zagairy. Simple rules for passive diffusion through the nuclear. Nuclear pore complexes npcs regulate bidirectional transport between the nucleus and the cytoplasm.
Traffic between the nucleus and the cytoplasm is accomplished through specialized, circular apertures that occur at sites where the inner and outer nuclear. To test this hypothesis, we studied the mutual effects between transporting molecules utilizing either the same or different modes of translocation. The nuclear pore complex npc is the proteinaceous nanopore that solely mediates molecular transport across the nuclear envelope between the nucleus and cytoplasm of a eukaryotic cell. Rout abstract although the nuclear pore complex npc is best known for its primary function as the key regulator of molecular traffic between the cytoplasm and the nucleus, a growing. Charge as a s election criterion for tr anslocation through. Transport routes through the nuclear pore complex pemberton, blobel and rosenblum 395 thus, two karyopherins that function in nuclear export have been identified. The molecular mechanism of translocation through the. An agentbased model for mrna export through the nuclear. However the genetic material in the nucleus is not totally isolated from the rest of the cell. Structure article transport related structures and processes of the nuclear pore complex studied through molecular dynamics lingling miao1 and klaus schulten1, 1beckman institute for advanced science and technology and department of physics, university of illinois at urbanachampaign, urbana. Transported proteins interact with a set of 20 transport receptors, importins and exportins, which mediate translocation through the nuclear pore complex.
Force triggers yap nuclear entry by regulating transport. Transport of macromolecules across the nuclear envelope is an active process that depends on soluble factors including the gtpase ran. Molecular transport between the cytoplasm and the nucleoplasm is gated by highly selective nuclear pore complexes npcs. Npcs provide access to the nucleus and regulate the transport of proteins and rna across the nuclear envelope. Exchange of macromolecules between the nucleus and cytoplasm is a key regulatory event in the expression of a cells genome. Nuclear transport under these conditions was blocked by calmodulin inhibitors. Aug 31, 2001 nuclear pore complexes, the conduits for information exchange between the nucleus and cytoplasm, appear broadly similar in eukaryotes from yeast to human. In higher eukaryotes, the npc and the ne disassemble and reassemble during cell division and livecell imaging has been a powerful tool to analyze these dynamic processes. The nuclear pore complex npc mediates selective transport across the nuclear envelope ne and plays crucial roles in several additional cellular functions. Components and regulation of nuclear transport processes. In addition, immunoblotting reveals the presence of soluble transport receptors and factors known to play important roles in the transport of macromolecules through the pore.
Nevertheless, the inverted transport assay presented here reveals important principles about the translocation reaction through the nuclear pore, and it will be interesting to test whether this assay will provide a more general tool to study complex nuclear export events. The mechanism underlying selective transport through the npc is still debated. The direction of transport through the nuclear pore can be. Signalmediated transport through nuclear pore complexes.
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