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CELL SCIENCE AT A GLANCE

The nuclear pore complex – structure and function at a glance

Greg Kabachinski and Thomas U. Schwartz*

ABSTRACT

Nuclear pore complexes (NPCs) are indispensable for cell function

and are at the center of several human diseases. NPCs provide

access to the nucleus and regulate the transport of proteins and

RNA across the nuclear envelope. They are aqueous channels

generated from a complex network of evolutionarily conserved

proteins known as nucleporins. In this Cell Science at a Glance

article and the accompanying poster, we discuss how transport

between the nucleoplasm and the cytoplasm is regulated, what we

currently know about the structure of individual nucleoporins and

the assembled NPC, and how the cell regulates assembly and

disassembly of such a massive structure. Our aim is to provide a

general overview on what we currently know about the nuclear pore

and point out directions of research this area is heading to.

KEY WORDS: Nuclear pore complex, Nucleus, Transport

IntroductionA defining difference between eukaryotic and prokaryotic cells is

the evolution of an endomembrane system and the presence of a

nucleus, resulting in the separation of the genetic material from

the rest of the cell. By restricting access to the nucleus and

separating gene transcription from protein translation, eukaryotic

cells have evolved to control gene expression in a highly

regulated manner. Although separated by the double-membrane

nuclear envelope, the interior of the nucleus is not completely

Department of Biology, Massachusetts Institute of Technology, 77 MassachusettsAvenue, Cambridge, MA 02139, USA.

*Author for correspondence (tus@mit.edu)

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isolated. Embedded throughout the nuclear envelope are largeprotein complexes known as nuclear pore complexes (NPCs) thatsit in circular openings where the outer nuclear membrane isfused with the inner nuclear membrane. Proteins and RNA can

cross the nuclear envelope in a tightly regulated process bytraveling through these aqueous protein channels. NPCs areconsidered to be the gatekeepers of the nucleus and facilitate

almost all transport between the nucleoplasm and cytoplasm.The nuclei of HeLa cells – the commonly used human tissue

culture cell line – contain on average 3000 NPCs (Dultz and

Ellenberg, 2010; Maul et al., 1972). A single NPC comprises,500, mainly evolutionarily conserved, individual proteinmolecules that are collectively known as nucleoporins (Nups)

(Alber et al., 2007). A fully assembled human NPC has anestimated molecular mass of ,125 MDa (Reichelt et al., 1990),making it one of the largest protein complexes in the cell. Despiteits size, the NPC is generated from a limited number of Nups (,30)

that appear in multiple copies (see poster, ‘NPC composition andNPC-deletion phenotypes’). Since the discovery of the NPC morethan 60 years ago (Callan and Tomlin, 1950), much has been

learned about its composition, structure and function.In this Cell Science at a Glance article and accompanying

poster, we examine how nuclear transport is regulated and

highlight the key differences between the transport requirementsof proteins and different types of RNA. We discuss some

common protein folds found in many Nups and how theycontribute to the overall NPC structure and barrier function,before discussing recent discoveries that show evolutionary linksbetween Nups and vesicle coats, and Nups and nuclear transport

receptors (NTRs) (see Box 1). Finally, we will review how thecell orchestrates and regulates the assembly of the NPC atdifferent times in the cell cycle. For the purpose of readability, we

predominantly use the human nucleoporin nomenclature toaddress those evolutionarily conserved properties of the NPCthat are likely to apply to NPCs of all eukaryotes; we use the

fungal nomenclature only when addressing specific aspects thatare different when comparing eukaryotic lineages. A briefoverview of NPC function, structure and assembly is provided,

and more-detailed reviews regarding specific aspects of NPCbiology are referenced throughout the text.

The nuclear import–export cycleWhereas metabolites, ions and molecules smaller than ,40 kDacan pass freely across the nuclear envelope, larger macromolecules(e.g. proteins, mRNA, tRNA, ribosome subunits and viruses)

typically cannot diffuse, but must be actively transported throughthe NPC (Gorlich and Kutay, 1999; Weis, 2003). Each class ofmacromolecule has a specific way in which it is transported across

the nuclear envelope.The import and export of proteins across the nuclear membrane

is regulated by a cycle of interactions between protein cargo,

NTRs (e.g. importins, exportins, transportins and karyopherins)and the small GTPase Ran, which regulates the ability of bothimportins and exportins to transport their cargo (see poster‘Nuclear import and export pathways – an overview’). For a

protein to actively pass through the NPC, it must contain anuclear localization signal (NLS) sequence. Although the NLScan be complex, the classic NLS is a stretch of basic residues (i.e.

KKKRK) (Kalderon et al., 1984). Simply adding an NLS to anon-nuclear protein is often sufficient to localize that protein intothe nucleus (Goldfarb et al., 1986). Recognition of the NLS of a

cargo is the first step in assembling an import-complex.Canonical nuclear import involves the recognition of the NLSby the adaptor protein importin-a, followed by binding of thekaryopherin importin-b, thereby forming a trimeric import

complex (Cook et al., 2007; Fried and Kutay, 2003; Stewart,2007b). Importin-b acts as the transport factor and carries thecargo through the NPC. In other cases, such as when the cargo

contains an atypical NLS, importin-b binds to the cargo directly(Cingolani et al., 2002; Lee et al., 2006; Lee et al., 2003).Through either direct interaction with the NLS or through an

adaptor protein, the NTRs ultimately determine which cargo ispermitted to pass through the nuclear pore.

Fluorescent microscopy studies have shown that translocation

through the pore is a rapid process with first-order kinetics, whichoccurs at a rate of ,1000 translocations every second (Ribbeckand Gorlich, 2001; Yang et al., 2004). Interestingly, the pore itselfdoes not determine the directionality of the import complex. In

fact, the movement of the import complex within the pore appearsto be random. The directionality of cargo import is determined bya gradient of nuclear RanGTP. Once an import complex enters

the nucleus, RanGTP binds importin-b, which releases the cargo.The importin-b–RanGTP complex itself is transported back to thecytosol, disassembled by GTP hydrolysis and ready for the next

round of import. Because a dynamic equilibrium of the import

Box 1. Evolution of the NPCIn addition to the architectural information gained from high-resolution structural studies of the NPC, these experiments havealso shed light on the evolution of Nups and the NPC as a whole. Ithas been hypothesized that the NPC shares common ancestry withvesicle coat complexes, including COPI, COPII and clathrin (Devoset al., 2004). This hypothesis was initially supported by predictionsthat similar elements of protein structures are found in both vesiclecoats and NPCs – mainly b-propellers and a-helical solenoids –and the fact that Sec13 is a bona fide member of both the NPC anda vesicle coat complex (COPII). The proposed evolution from acommon ancestor gained further support from high-resolutionstructural studies, which found that – despite having lesssequence similarity – several Nups (Nup85, Nup96, Nup93 andNup107) as well as vesicle coat proteins (Sec31 and Sec16)contain a conserved tripartite element, the so-called ancestralcoatomer element 1 (ACE1) (Brohawn et al., 2008).Recently, an additional evolutionary link between the NPC and

NTRs has been uncovered. The defining characteristic of thekaryopherin protein family, which includes importin-a, importin-band the exportins, is that they all contain superhelical stacked a-helical units, which allows them to interact with FG-repeats andshuttle cargo through the NPC. Structural analysis of Nup188 (M.

thermophile) and its mammalian homolog Nup205 (Nup192 in S.

cerevisiae and Chaetomium thermophilium), members of theNup93 subcomplex, showed they also adopt a structure ofstacked a-helices (Andersen et al., 2013; Flemming et al., 2012;Sampathkumar et al., 2013; Stuwe et al., 2014). Such superhelicalstructures are abundant in eukaryotic cells and are used in manyfunctional contexts. However, similar to karyopherins, Nup188 andNup205/192 were both shown to specifically bind to FG-repeatsand to be able to transverse the NPC, characteristics typicallyassociated with NTRs (Andersen et al., 2013).The evolutionary links between the NPC, coat-proteins and

transport receptors that have been provided by high-resolutionstructural studies might help to better understand how the NPC isformed, how Nups interact with each other and, ultimately, howeach Nup functions in nuclear transport.

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complex is maintained in the pore, disassembly of the complex inthe nucleus results in a net flow of cargo towards the

nucleoplasm. This directional flow is dependent on a RanGTPgradient, whereby the concentration of RanGTP is greater in thenucleus than in the cytosol. This RanGTP gradient is maintainedby a Ran guanine nucleotide exchange factor (GEF) that is

preferentially located in the nucleus and by RanGTPase-activating proteins (GAPs) in the cytosol (Stewart, 2007b).

Conceptually, the export of proteins from the nucleus occurs in

an process that is analogous to nuclear import but reversed (seeposter, ‘Nuclear import and export pathways – an overview’).An export complex forms inside the nucleus between cargo

displaying a nuclear export signal (NES) – typically a sequencethat is leucine rich – a cognate export karyopherin and RanGTP(Ossareh-Nazari et al., 2001). This ternary export complex enters

the NPC and, upon exiting the nuclear pore, encounters RanGAP –the Ran-specific GTPase-activating protein – that catalyzes GTPhydrolysis, resulting in disassembly and the release of the cargo(Cook et al., 2007). Also here, the established RanGTP gradient is

the driving force for the directionality and nuclear export ofproteins.

RNA exportThe export of some classes of RNA is similar to the export ofproteins. For example, tRNAs and small nuclear RNAs (snRNAs)

use the RanGTP gradient and are transported through the NPC bytheir specific karyopherins exportin-t and Crm1, respectively(Cook and Conti, 2010; Rodriguez et al., 2004). The export of

mature ribosomal subunits is also dependent on the RanGTPgradient and uses karyopherin-like transport receptors. However,because of the size of the ribosome, the precise process is stillunder intense investigation and, overall, remains poorly

understood (Panse and Johnson, 2010; Tschochner and Hurt,2003; Zemp and Kutay, 2007).

The export of mRNA is considerably different from that of

proteins and other RNAs. mRNA is not exported alone but,instead, as a large messenger ribonucleoprotein (mRNP)complex, in which a single mRNA molecule is surrounded by

hundreds of proteins that have a function in processing, capping,splicing and polyadenylation. The export of mRNPs, thus,presents the cell with a new set of challenges because (1) thediameter of the mRNP cargo is extremely large, (2) the cell must

be able to distinguish between correctly (mature) and incorrectly(immature) packaged RNPs, and (3) the mRNA within the RNPmay adopt topologies that need to be remodeled before translation

can occur (Grunwald et al., 2011).To overcome these unique challenges, cells have developed a

separate mode for transport of mRNPs through the NPC. Before

an mRNP particle can enter the NPC, a quality control step isperformed by members of the TRAMP (Trf4–Air2–Mtr4ppolyadenylation) and exosome protein complexes, which survey

mRNA, and identify and degrade any defective mRNPs(Chlebowski et al., 2013; Makino et al., 2013). A maturemRNP is then recruited to the nucleoplasmic side of the NPC or –more specifically – the nuclear basket (see below) by the TREX2

(transcription-export complex 2) and THO complexes. Thisoccurs co-transcriptionally and TREX2 and THO complexesare, therefore, essential in linking active gene transcription to

mRNA export (Kohler and Hurt, 2007).Once a mature mRNP is assembled and targeted to the NPC, it

is transported through the channel by a non-karyopherin transport

receptor, the Nxf1–Nxt1 heterodimer (Mex67-Mtr2 in yeast)

(Gruter et al., 1998; Segref et al., 1997; Stewart, 2010). Althoughthe exact stoichiometry is unknown, several Nxf1–Nxt1

heterodimers bind to the mRNP. Nxf1 and Mex67 neither bindto Ran nor do they use the RanGTP gradient that is crucial forprotein transport. Instead, mRNA export (see poster, ‘Export ofmRNPs’) is driven by ATP rather than GTP hydrolysis. The

energy is required to establish transport directionality byremodeling the mRNP once it reaches the cytoplasm (Stewart,2007a). Inside the central NPC channel, the mRNP can move

forward and backward. However, once part of the mRNP reachesthe cytoplasmic face of the NPC, the DEAD-box RNA helicaseDbp5 (also known as SON in humans), whose activity is

regulated by the nucleoporin Gle1 and inositol hexaphosphate(IP6), binds to the mRNA and alters the structure of the mRNP,thereby removing the transport receptor Nxf1–Nxt1 heterodimer

in an ATP-dependent manner (Montpetit et al., 2011; Tran et al.,2007; Weirich et al., 2006). Removal of Nxf1–Nxt1 prevents therespective part of the mRNP from returning to the centralchannel. By repeating this process, the mRNP is fully extracted

out of the pore into the cytoplasm. For a more in-depth review ofthe process, see (Bonnet and Palancade, 2014; Oeffinger andZenklusen, 2012).

The FG barrierThe NPC is an extremely versatile protein complex as it has to

enable the selective transport of both proteins and mature RNAwith sizes that range from 40 kDa to entire ribosomal subunits,while preventing other molecules of similar sizes from passing.

How does the NPC create a barrier while regulating nucleartransport? This question still remains an intensely debated topicin the field. One issue that is agreed upon is that the regulatoryfunction of the NPC is achieved by a subset of specific Nups,

collectively known as FG-Nups. FG-Nups typically contain astructured domain that serves as an NPC anchor point, fromwhich a largely unstructured, filamentous and hydrophilic

extension emanates, which is studded with multiple (5–50)hydrophopic phenylalanine–glycine (FG)-repeats (Terry andWente, 2009).

Over the past decade, a number of models have been proposedon how FG-Nups form the transport barrier (Lim et al., 2007;Patel et al., 2007; Peters, 2005; Ribbeck et al., 2002; Rout et al.,2003). Recent work has provided strong evidence for the so-

called ‘selective-phase model’ (Hulsmann et al., 2012; Labokhaet al., 2013). In this model, FG-Nups line the central channel andextend their FG-repeat regions into the middle of the channel.

The high local concentration of FG-repeats due to the many FG-Nups that localize to the channel (,200 FG-Nups per channel)generates a hydrogel, in which the FG-repeats bind cohesively to

form a ‘sieve’ with mesh size of ,5 nm. A macromolecule largerthan ,5 nm (,40 kDa) passes through this barrier by means of atransport receptor that has the ability to bind the FG-repeats,

thereby locally ‘melting’ the FG-mediated sieve. The selective-phase model has shortcomings because it does not yet explain theinterplay between the different FG nucleoporins; moreover, it islargely based on in vitro data using one FG-protein at the time.

Also, many FG-Nups are – for so-far-unknown reasons – heavilyglycosylated. Finally, the influence of NTRs as possibleconstitutive elements of the FG barrier is still mostly

unexplored. Thus, the FG barrier remains a central researchtopic that is passionately and controversially discussed (Atkinsonet al., 2013; Kapinos et al., 2014; Peters, 2009; Yamada et al.,

2010; Zilman et al., 2010).

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NPC structureThe NPC is one of the largest protein complexes in the cell and

easily recognizable using scanning electron microscopy (EM). EarlyEM studies revealed an eightfold rotational ring symmetry for theentire structure. In addition, the main NPC structure contains ringsthat are situated on its cytoplasmic and nucleoplasmic sides, giving

the NPC an apparent twofold symmetry across the nuclearmembrane (Beck et al., 2004; Stoffler et al., 2003). A recentelectron tomographic study has delineated the structure of the core

NPC scaffold at a resolution of 3.2 nm (Bui et al., 2013). This work,together with other studies, shows that the NPC has a thickness of,50 nm, an outer diameter of ,80–120 nm and an inner diameter

of ,40 nm (Bui et al., 2013; Grossman et al., 2012; Maimon et al.,2012). In addition, the obtained images reveal that the NPC containsa structure, resembling a basket that extends into the nucleoplasm

(the nuclear basket) and filaments that extend into the cytoplasm(referred to as cytoplasmic filaments).

Despite its enormous size, the NPC is made up of only ,30Nups that are largely conserved throughout eukaryotic evolution

(Cronshaw et al., 2002; DeGrasse et al., 2009; Rout et al., 2000).Nups are organized into subcomplexes that are biochemicallydefined by their affinity to each other. In humans, the Nup62

complex comprises Nup62, Nup58 (Uniprot ID: Q9BVL2) andNup54, all of which contain FG-repeats and are found in thecentral pore (Finlay et al., 1991; Grandi et al., 1993; Hu et al.,

1996) (see poster, ‘NPC composition and NPC-deletionphenotypes’, for corresponding Nup nomenclature in buddingyeast Saccharomyces cerevisiae). Nup62 is also a member of the

human Nup214 subcomplex, where it interacts with Nup88 andthe FG-containing Nup214, and is located on the cytoplasmic sideof the NPC (Fornerod et al., 1997; Macaulay et al., 1995). Twoother essential subcomplexes provide the structural scaffold for

the entire NPC and serve as adaptor proteins that link the FG-Nups to the nuclear membrane. The first is the Y-complex that, inseveral EM studies, was shown to be elongated and branched,

resembling the letter Y – hence its name (Bui et al., 2013;Kampmann and Blobel, 2009; Lutzmann et al., 2002). In humans,this subcomplex contains ten proteins, Nup107, Nup85, Nup96,

Nup160, Nup133, Sec13, Seh1, Nup37, Nup43 and ELYS(Loıodice et al., 2004; Lutzmann et al., 2002; Rasala et al.,2006; Siniossoglou et al., 1996). Another NPC subcomplex is theNup93 complex, which comprises Nup93, Nup188, Nup205,

Nup155 and Nup35 in humans (Vollmer and Antonin, 2014).Although the structure of the entire Nup93 subcomplex is stillunknown, the individual structures of all its components have

been published. Surprisingly, even though the NPC spans twomembranes (the outer- and inner-nuclear membrane), only four ofthe human Nups contain transmembrane (TM) domains, namely

Ndc1, Gp210, TMEM33 and Pom121. Biochemical data indicatethat these TM proteins connect to the NPC scaffold through theNup93 complex (Eisenhardt et al., 2014; Mitchell et al., 2010;

Yavuz et al., 2010).A high-resolution structure of the NPC, in which the position

of each individual protein is resolved, is a formidable goal forstructural biologists. Efforts over the past decade have shown

that a hybrid approach using different experimental andcomputational methods is likely to be needed to fulfill this goal(Alber et al., 2007; Bui et al., 2013).

Assembly and disassembly of the NPCIn addition to being one of the largest protein complexes in the

cell, the structural scaffold of the NPC is also one of the longest

lived (Savas et al., 2012). Whereas most mammalian proteinshave an average half-life of a few days (Cambridge et al., 2011;

Price et al., 2010), recent whole animal pulse-chase experimentsdemonstrated that, in postmitotic tissues, the structural scaffold ofthe NPC, or at least components thereof, persists over the entirelifetime of a cell (Toyama et al., 2013). In dividing cells, NPCs

undergo a cycle of assembly and disassembly that is in concertwith the cell cycle. NPC assembly occurs during two stages of thecell cycle, in interphase and immediately after mitosis.

During interphase, the nuclear envelope increases its surfacearea, and the number of NPCs doubles in preparation for mitosisand to allow the cell to handle the concomitant increase in

transcription that necessitates additional mRNA export as well assynthesis and import of histones. These new NPCs form de novo

and assemble from both sides of the intact nuclear envelope

(D’Angelo et al., 2006).A model for NPC assembly in interphase has been proposed on

the basis of several studies, in which the members of the Nup93subcomplex are first recruited to the TM-Nups (Flemming et al.,

2009; Makio et al., 2009; Onischenko et al., 2009). Thisassociation, facilitated by membrane-deforming proteins (e.g.reticulons) then bends the outer- and inner-nuclear membrane

toward each other until they eventually fuse (Dawson et al.,2009). Live-imaging kinetics studies have shown that members ofthe Y-complex also appear around this time (Dultz and Ellenberg,

2010). The localization of the Y-complex during assembly, andNPC assembly itself, is dependent on the components of the Rancycle and importin-b (D’Angelo et al., 2006; Ryan and Wente,

2002; Ryan et al., 2003; Ryan et al., 2007). Finally, after all thescaffolding Nups have been assembled, the FG-Nups arelocalized to the NPC, generating the transport barrier.

For post-mitotic NPCs assembly it is important to consider the

vast differences between the fate of the nuclear envelope indifferent organisms. In S. cerevisiae, the nuclear enveloperemains closed throughout mitosis, as the microtubule

organizing center (MTOC) is embedded in it. In many otherorganisms, MTOCs are cytoplasmic, which necessitates thenuclear envelope to break down for correct chromosome

segregation to occur. Between these extremes of ‘open’ and‘closed’ mitosis, there are a number of cell types that undergovariations of a ‘semi-closed’ mitosis (De Souza and Osmani,2007; Guttinger et al., 2009). To what extend these variations

affect NPC dissembly and/or reassembly, and how this mighthave generated fundamentally different post-mitotic versusinterphase assembly pathways is an ongoing discussion

(D’Angelo and Hetzer, 2008; Doucet et al., 2010). However, itis clear that NPCs are fully disassembled during open mitosis(Laurell et al., 2011) and partially disassembled during ‘semi-

closed’ mitosis (De Souza et al., 2004).Post-mitotic assembly of NPCs begins at the same time as the

nuclear envelope starts to reform (Schooley et al., 2012). This

assembly process is proposed to be initiated by the targeting ofthe Y-complex to chromatin, which is facilitated by small-DNA-binding motifs (AT hooks) that are predicted to be present inELYS (Rasala et al., 2008). As with NPC assembly during

interphase, Ran – as well as its effectors – and importin-bregulate Nup recruitment to chromatin (Harel et al., 2003;Walther et al., 2003). However, once ELYS is localized to

chromatin, assembly continues with the remainder of the Nup107subcomplex, which interacts with the TM-Nups Ndc1 andPom121 (Dultz et al., 2008; Rasala et al., 2008). Members of

the Nup93 subcomplex are then recruited soon after (Dultz et al.,

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2008) and thought to assist in membrane fusion and porestabilization (Eisenhardt et al., 2014; Rodenas et al., 2009). Once

all the scaffolding Nups have been incorporated into the pore, theFG-Nups are localized and nuclear pore activity is restored (Dultzet al., 2008).

Despite the overall stability of the NPC in non-dividing cells,

NPCs must nevertheless disassemble in order for mitosis toproceed in dividing cells. NPC disassembly is fast and occurs in astepwise-regulated manner. Although the exact steps and order in

which they occur are currently unknown, disassembly does notappear to be a simple reversal of the assembly steps describedabove (Dultz et al., 2008). The trigger to initiate the disassembly

process is the phosphorylation of several Nups by mitotic kinases(e.g. Cdk1) (Glavy et al., 2007; Laurell et al., 2011; Onischenkoet al., 2005). Following their phosphorylation and release from

the NPC, some nuclear pore subcomplexes also have additionalroles in mitosis. For example, the Y subcomplex is localized tokinetochores, and regulates mitotic spindle assembly andchromosome congression (Orjalo et al., 2006; Zuccolo et al.,

2007).

PerspectivesThe NPC is a multifaceted and intricate protein complex that isessential to all eukaryotic life. In addition to the main function ofthe Nups in nucleocytoplasmic transport, new roles – especially in

the regulation of gene expression – have recently been identified(Texari et al., 2013; Van de Vosse et al., 2013). Therefore, it is notsurprising that aberrant functions of Nups and NPCs have been

implicated in many and diverse human pathologies, includingautoimmune diseases, viral infections, cardiomyopathies andvarious cancers (Capelson and Hetzer, 2009; Chow et al., 2012;

Hatch and Hetzer, 2014; Simon and Rout, 2014). To betterunderstand large, complicated protein complexes such as theNPC, a multipronged approach using hybrid methods is needed.Already, single-particle EM, EM tomography, super-resolution

microscopy, crystallography, immunoprecipitation, crosslinking,mass spectrometry and numerous other methods are being used andcombined to help to generate a highly detailed model of the NPC

and to identify so-far-unknown Nup functions. Given the intensityof research in the field, it seems realistic that we might know thestructure of the NPC, including the positions of all scaffold

nucleoporins in the foreseeable future. This, in turn, will giveresearchers the opportunity to specifically address the manyaspects of NPC biology, which will no doubt disclose exciting

secrets of cell biology.

AcknowledgementsWe apologize to the authors whose work we were unable to cite due to spacelimitations. We thank Allyson Anding for her help in generating some of thefigures, Kasper Anderson for critically reading the manuscript and Martin Beck forproviding the tomographic figure.

Competing interestsThe authors declare no competing or financial interests.

FundingThis work of our laboratory was supported by the National Institutes of Health [grantnumber GM077537] to T.U.S. Deposited in PMC for release after 12 months.

Cell science at a glanceA high-resolution version of the poster is available for downloadingin the online version of this article at jcs.biologists.org. Individualposter panels are available as JPEG files athttp://jcs.biologists.org/lookup/suppl/doi:10.1242/jcs.083246/-/DC2.

ReferencesAlber, F., Dokudovskaya, S., Veenhoff, L. M., Zhang, W., Kipper, J., Devos, D.,Suprapto, A., Karni-Schmidt, O., Williams, R., Chait, B. T. et al. (2007). Themolecular architecture of the nuclear pore complex. Nature 450, 695-701.

Andersen, K. R., Onischenko, E., Tang, J. H., Kumar, P., Chen, J. Z., Ulrich, A.,Liphardt, J. T., Weis, K. and Schwartz, T. U. (2013). Scaffold nucleoporinsNup188 and Nup192 share structural and functional properties with nucleartransport receptors. eLife 2, e00745.

Atkinson, C. E., Mattheyses, A. L., Kampmann, M. and Simon, S. M. (2013).Conserved spatial organization of FG domains in the nuclear pore complex.Biophys. J. 104, 37-50.

Beck, M., Forster, F., Ecke, M., Plitzko, J. M., Melchior, F., Gerisch, G.,Baumeister, W. and Medalia, O. (2004). Nuclear pore complex structure anddynamics revealed by cryoelectron tomography. Science 306, 1387-1390.

Bonnet, A. and Palancade, B. (2014). Regulation of mRNA trafficking by nuclearpore complexes. Genes (Basel) 5, 767-791.

Brohawn, S. G., Leksa, N. C., Spear, E. D., Rajashankar, K. R. and Schwartz,T. U. (2008). Structural evidence for common ancestry of the nuclear porecomplex and vesicle coats. Science 322, 1369-1373.

Bui, K. H., von Appen, A., DiGuilio, A. L., Ori, A., Sparks, L., Mackmull, M. T.,Bock, T., Hagen, W., Andres-Pons, A., Glavy, J. S. et al. (2013). Integratedstructural analysis of the human nuclear pore complex scaffold. Cell 155, 1233-1243.

Callan, H. G. and Tomlin, S. G. (1950). Experimental studies on amphibianoocyte nuclei. I. Investigation of the structure of the nuclear membrane bymeans of the electron microscope. Proc. R. Soc. B 137, 367-378.

Cambridge, S. B., Gnad, F., Nguyen, C., Bermejo, J. L., Kruger, M. and Mann,M. (2011). Systems-wide proteomic analysis in mammalian cells revealsconserved, functional protein turnover. J. Proteome Res. 10, 5275-5284.

Capelson, M. and Hetzer, M. W. (2009). The role of nuclear pores in generegulation, development and disease. EMBO Rep. 10, 697-705.

Chlebowski, A., Lubas, M., Jensen, T. H. and Dziembowski, A. (2013). RNAdecay machines: the exosome. Biochim. Biophys. Acta 1829, 552-560.

Chow, K.-H., Factor, R. E. and Ullman, K. S. (2012). The nuclear envelopeenvironment and its cancer connections. Nat. Rev. Cancer 12, 196-209.

Cingolani, G., Bednenko, J., Gillespie, M. T. and Gerace, L. (2002). Molecularbasis for the recognition of a nonclassical nuclear localization signal by importinbeta. Mol. Cell 10, 1345-1353.

Cook, A. G. and Conti, E. (2010). Nuclear export complexes in the frame. Curr.Opin. Struct. Biol. 20, 247-252.

Cook, A., Bono, F., Jinek, M. and Conti, E. (2007). Structural biology ofnucleocytoplasmic transport. Annu. Rev. Biochem. 76, 647-671.

Cronshaw, J. M., Krutchinsky, A. N., Zhang, W., Chait, B. T. and Matunis, M. J.(2002). Proteomic analysis of the mammalian nuclear pore complex. J. Cell Biol.158, 915-927.

D’Angelo, M. A. and Hetzer, M. W. (2008). Structure, dynamics and function ofnuclear pore complexes. Trends Cell Biol. 18, 456-466.

D’Angelo, M. A., Anderson, D. J., Richard, E. and Hetzer, M. W. (2006). Nuclearpores form de novo from both sides of the nuclear envelope.Science 312, 440-443.

Dawson, T. R., Lazarus, M. D., Hetzer, M. W. and Wente, S. R. (2009). ERmembrane-bending proteins are necessary for de novo nuclear pore formation.J. Cell Biol. 184, 659-675.

De Souza, C. P. C. and Osmani, S. A. (2007). Mitosis, not just open or closed.Eukaryot. Cell 6, 1521-1527.

De Souza, C. P. C., Osmani, A. H., Hashmi, S. B. and Osmani, S. A. (2004).Partial nuclear pore complex disassembly during closed mitosis in Aspergillusnidulans. Curr. Biol. 14, 1973-1984.

DeGrasse, J. A., DuBois, K. N., Devos, D., Siegel, T. N., Sali, A., Field, M. C.,Rout, M. P. and Chait, B. T. (2009). Evidence for a shared nuclear porecomplex architecture that is conserved from the last common eukaryoticancestor. Mol. Cell. Proteomics 8, 2119-2130.

Devos, D., Dokudovskaya, S., Alber, F., Williams, R., Chait, B. T., Sali, A. andRout, M. P. (2004). Components of coated vesicles and nuclear pore complexesshare a common molecular architecture. PLoS Biol. 2, e380.

Doucet, C. M., Talamas, J. A. and Hetzer, M. W. (2010). Cell cycle-dependentdifferences in nuclear pore complex assembly in metazoa. Cell 141, 1030-1041.

Dultz, E. and Ellenberg, J. (2010). Live imaging of single nuclear pores revealsunique assembly kinetics and mechanism in interphase. J. Cell Biol. 191, 15-22.

Dultz, E., Zanin, E., Wurzenberger, C., Braun, M., Rabut, G., Sironi, L. andEllenberg, J. (2008). Systematic kinetic analysis of mitotic dis- and reassemblyof the nuclear pore in living cells. J. Cell Biol. 180, 857-865.

Eisenhardt, N., Redolfi, J. and Antonin, W. (2014). Interaction of Nup53 withNdc1 and Nup155 is required for nuclear pore complex assembly. J. Cell Sci.127, 908-921.

Finlay, D. R., Meier, E., Bradley, P., Horecka, J. and Forbes, D. J. (1991). Acomplex of nuclear pore proteins required for pore function. J. Cell Biol. 114,169-183.

Flemming, D., Sarges, P., Stelter, P., Hellwig, A., Bottcher, B. and Hurt, E.(2009). Two structurally distinct domains of the nucleoporin Nup170 cooperateto tether a subset of nucleoporins to nuclear pores. J. Cell Biol. 185, 387-395.

Flemming, D., Devos, D. P., Schwarz, J., Amlacher, S., Lutzmann, M. and Hurt,E. (2012). Analysis of the yeast nucleoporin Nup188 reveals a conserved S-likestructure with similarity to karyopherins. J. Struct. Biol. 177, 99-105.

CELL SCIENCE AT A GLANCE Journal of Cell Science (2015) 128, 423–429 doi:10.1242/jcs.083246

427

Jour

nal o

f Cel

l Sci

ence

Fornerod, M., van Deursen, J., van Baal, S., Reynolds, A., Davis, D., Murti,K. G., Fransen, J. and Grosveld, G. (1997). The human homologue of yeastCRM1 is in a dynamic subcomplex with CAN/Nup214 and a novel nuclear porecomponent Nup88. EMBO J. 16, 807-816.

Fried, H. and Kutay, U. (2003). Nucleocytoplasmic transport: taking an inventory.Cell. Mol. Life Sci. 60, 1659-1688.

Glavy, J. S., Krutchinsky, A. N., Cristea, I. M., Berke, I. C., Boehmer, T., Blobel,G. and Chait, B. T. (2007). Cell-cycle-dependent phosphorylation of thenuclear pore Nup107-160 subcomplex. Proc. Natl. Acad. Sci. USA 104, 3811-3816.

Goldfarb, D. S., Gariepy, J., SCHOOLNIK, G., AND KORNBERG, R. D. (1986).Synthetic peptides as nuclear localization signals. Nature 322, 641-644.

Gorlich, D. and Kutay, U. (1999). Transport between the cell nucleus and thecytoplasm. Annu. Rev. Cell Dev. Biol. 15, 607-660.

Grandi, P., Doye, V. and Hurt, E. C. (1993). Purification of NSP1 reveals complexformation with ‘GLFG’ nucleoporins and a novel nuclear pore protein NIC96.EMBO J. 12, 3061-3071.

Grossman, E., Medalia, O. and Zwerger, M. (2012). Functional architecture ofthe nuclear pore complex. Annu. Rev. Biophys. 41, 557-584.

Grunwald, D., Singer, R. H. and Rout, M. (2011). Nuclear export dynamics ofRNA-protein complexes. Nature 475, 333-341.

Gruter, P., Tabernero, C., von Kobbe, C., Schmitt, C., Saavedra, C., Bachi, A.,Wilm, M., Felber, B. K. and Izaurralde, E. (1998). TAP, the human homolog ofMex67p, mediates CTE-dependent RNA export from the nucleus. Mol. Cell 1,649-659.

Guttinger, S., Laurell, E. and Kutay, U. (2009). Orchestrating nuclear envelopedisassembly and reassembly during mitosis. Nat. Rev. Mol. Cell Biol. 10, 178-191.

Harel, A., Chan, R. C., Lachish-Zalait, A., Zimmerman, E., Elbaum, M. andForbes, D. J. (2003). Importin beta negatively regulates nuclear membranefusion and nuclear pore complex assembly. Mol. Biol. Cell 14, 4387-4396.

Hatch, E. and Hetzer, M. (2014). Breaching the nuclear envelope in developmentand disease. J. Cell Biol. 205, 133-141.

Hu, T., Guan, T. and Gerace, L. (1996). Molecular and functional characterizationof the p62 complex, an assembly of nuclear pore complex glycoproteins. J. CellBiol. 134, 589-601.

Hulsmann, B. B., Labokha, A. A. and Gorlich, D. (2012). The permeability ofreconstituted nuclear pores provides direct evidence for the selective phasemodel. Cell 150, 738-751.

Kalderon, D., Roberts, B. L., Richardson, W. D. and Smith, A. E. (1984). A shortamino acid sequence able to specify nuclear location. 39, 499-509.

Kampmann, M. and Blobel, G. (2009). Three-dimensional structure and flexibilityof a membrane-coating module of the nuclear pore complex. Nat. Struct. Mol.Biol. 16, 782-788.

Kapinos, L. E., Schoch, R. L., Wagner, R. S., Schleicher, K. D. and Lim, R. Y.H. (2014). Karyopherin-centric control of nuclear pores based on molecularoccupancy and kinetic analysis of multivalent binding with FG nucleoporins.Biophys. J. 106, 1751-1762.

Kohler, A. and Hurt, E. (2007). Exporting RNA from the nucleus to the cytoplasm.Nat. Rev. Mol. Cell Biol. 8, 761-773.

Labokha, A. A., Gradmann, S., Frey, S., Hulsmann, B. B., Urlaub, H., Baldus,M. and Gorlich, D. (2013). Systematic analysis of barrier-forming FG hydrogelsfrom Xenopus nuclear pore complexes. EMBO J. 32, 204-218.

Laurell, E., Beck, K., Krupina, K., Theerthagiri, G., Bodenmiller, B., Horvath,P., Aebersold, R., Antonin, W. and Kutay, U. (2011). Phosphorylation of Nup98by multiple kinases is crucial for NPC disassembly during mitotic entry. Cell 144,539-550.

Lee, S. J., Sekimoto, T., Yamashita, E., Nagoshi, E., Nakagawa, A., Imamoto,N., Yoshimura, M., Sakai, H., Chong, K. T., Tsukihara, T. et al. (2003). Thestructure of importin-beta bound to SREBP-2: nuclear import of a transcriptionfactor. Science 302, 1571-1575.

Lee, B. J., Cansizoglu, A. E., Suel, K. E., Louis, T. H., Zhang, Z. and Chook,Y. M. (2006). Rules for nuclear localization sequence recognition by karyopherinbeta 2. Cell 126, 543-558.

Lim, R. Y. H., Fahrenkrog, B., Koser, J., Schwarz-Herion, K., Deng, J. andAebi, U. (2007). Nanomechanical basis of selective gating by the nuclear porecomplex. Science 318, 640-643.

Loıodice, I., Alves, A., Rabut, G., Van Overbeek, M., Ellenberg, J., Sibarita,J.-B. and Doye, V. (2004). The entire Nup107-160 complex, including three newmembers, is targeted as one entity to kinetochores in mitosis. Mol. Biol. Cell 15,3333-3344.

Lutzmann, M., Kunze, R., Buerer, A., Aebi, U. and Hurt, E. (2002). Modular self-assembly of a Y-shaped multiprotein complex from seven nucleoporins. EMBOJ. 21, 387-397.

Macaulay, C., Meier, E. and Forbes, D. J. (1995). Differential mitotic phosphorylationof proteins of the nuclear pore complex. J. Biol. Chem. 270, 254-262.

Maimon, T., Elad, N., Dahan, I. and Medalia, O. (2012). The human nuclearpore complex as revealed by cryo-electron tomography. Structure 20, 998-1006.

Makino, D. L., Halbach, F. and Conti, E. (2013). The RNA exosome andproteasome: common principles of degradation control. Nat. Rev. Mol. Cell Biol.14, 654-660.

Makio, T., Stanton, L. H., Lin, C.-C., Goldfarb, D. S., Weis, K. and Wozniak,R. W. (2009). The nucleoporins Nup170p and Nup157p are essential for nuclearpore complex assembly. J. Cell Biol. 185, 459-473.

Maul, G. G., Maul, H. M., Scogna, J. E., Lieberman, M. W., Stein, G. S., Hsu,B. Y. and Borun, T. W. (1972). Time sequence of nuclear pore formation inphytohemagglutinin-stimulated lymphocytes and in HeLa cells during the cellcycle. J. Cell Biol. 55, 433-447.

Mitchell, J. M., Mansfeld, J., Capitanio, J., Kutay, U. and Wozniak, R. W.(2010). Pom121 links two essential subcomplexes of the nuclear pore complexcore to the membrane. J. Cell Biol. 191, 505-521.

Montpetit, B., Thomsen, N. D., Helmke, K. J., Seeliger, M. A., Berger, J. M. andWeis, K. (2011). A conserved mechanism of DEAD-box ATPase activation bynucleoporins and InsP6 in mRNA export. Nature 472, 238-242.

Oeffinger, M. and Zenklusen, D. (2012). To the pore and through the pore: a storyof mRNA export kinetics. Biochim. Biophys. Acta 1819, 494-506.

Onischenko, E. A., Gubanova, N. V., Kiseleva, E. V. and Hallberg, E. (2005).Cdk1 and okadaic acid-sensitive phosphatases control assembly of nuclearpore complexes in Drosophila embryos. Mol. Biol. Cell 16, 5152-5162.

Onischenko, E., Stanton, L. H., Madrid, A. S., Kieselbach, T. and Weis, K.(2009). Role of the Ndc1 interaction network in yeast nuclear pore complexassembly and maintenance. J. Cell Biol. 185, 475-491.

Orjalo, A. V., Arnaoutov, A., Shen, Z., Boyarchuk, Y., Zeitlin, S. G., Fontoura,B., Briggs, S., Dasso, M. and Forbes, D. J. (2006). The Nup107-160nucleoporin complex is required for correct bipolar spindle assembly. Mol. Biol.Cell 17, 3806-3818.

Ossareh-Nazari, B., Gwizdek, C. and Dargemont, C. (2001). Protein export fromthe nucleus. Traffic 2, 684-689.

Panse, V. G. and Johnson, A. W. (2010). Maturation of eukaryotic ribosomes:acquisition of functionality. Trends Biochem. Sci. 35, 260-266.

Patel, S. S., Belmont, B. J., Sante, J. M. and Rexach, M. F. (2007). Nativelyunfolded nucleoporins gate protein diffusion across the nuclear pore complex.Cell 129, 83-96.

Peters, R. (2005). Translocation through the nuclear pore complex: selectivity andspeed by reduction-of-dimensionality. Traffic 6, 421-427.

Peters, R. (2009). Translocation through the nuclear pore: Kaps pave the way.BioEssays 31, 466-477.

Price, J. C., Guan, S., Burlingame, A., Prusiner, S. B. and Ghaemmaghami, S.(2010). Analysis of proteome dynamics in the mouse brain. Proc. Natl. Acad.Sci. USA 107, 14508-14513.

Rasala, B. A., Orjalo, A. V., Shen, Z., Briggs, S. and Forbes, D. J. (2006). ELYSis a dual nucleoporin/kinetochore protein required for nuclear pore assemblyand proper cell division. Proc. Natl. Acad. Sci. USA 103, 17801-17806.

Rasala, B. A., Ramos, C., Harel, A. and Forbes, D. J. (2008). Capture of AT-richchromatin by ELYS recruits POM121 and NDC1 to initiate nuclear poreassembly. Mol. Biol. Cell 19, 3982-3996.

Reichelt, R., Holzenburg, A., Buhle, E. L., Jr, Jarnik, M., Engel, A. and Aebi, U.(1990). Correlation between structure and mass distribution of the nuclear porecomplex and of distinct pore complex components. J. Cell Biol. 110, 883-894.

Ribbeck, K. and Gorlich, D. (2001). Kinetic analysis of translocation throughnuclear pore complexes. EMBO J. 20, 1320-1330.

Ribbeck, K. and Gorlich, D. (2002). The permeability barrier of nuclear porecomplexes appears to operate via hydrophobic exclusion. EMBO J. 21, 2664-2671.

Rodenas, E., Klerkx, E. P. F., Ayuso, C., Audhya, A. and Askjaer, P. (2009).Early embryonic requirement for nucleoporin Nup35/NPP-19 in nuclearassembly. Dev. Biol. 327, 399-409.

Rodriguez, M. S., Dargemont, C. and Stutz, F. (2004). Nuclear export of RNA.Biol. Cell 96, 639-655.

Rout, M. P., Aitchison, J. D., Suprapto, A., Hjertaas, K., Zhao, Y. and Chait,B. T. (2000). The yeast nuclear pore complex: composition, architecture, andtransport mechanism. J. Cell Biol. 148, 635-652.

Rout, M. P., Aitchison, J. D., Magnasco, M. O. and Chait, B. T. (2003). Virtualgating and nuclear transport: the hole picture. Trends Cell Biol. 13, 622-628.

Ryan, K. J. and Wente, S. R. (2002). Isolation and characterization of newSaccharomyces cerevisiae mutants perturbed in nuclear pore complexassembly. BMC Genet. 3, 17.

Ryan, K. J., McCaffery, J. M. and Wente, S. R. (2003). The Ran GTPase cycle isrequired for yeast nuclear pore complex assembly. J. Cell Biol. 160, 1041-1053.

Ryan, K. J., Zhou, Y. and Wente, S. R. (2007). The karyopherin Kap95 regulatesnuclear pore complex assembly into intact nuclear envelopes in vivo. Mol. Biol.Cell 18, 886-898.

Sampathkumar, P., Kim, S. J., Upla, P., Rice, W. J., Phillips, J., Timney, B. L.,Pieper, U., Bonanno, J. B., Fernandez-Martinez, J., Hakhverdyan, Z. et al.(2013). Structure, dynamics, evolution, and function of a major scaffoldcomponent in the nuclear pore complex. Structure 21, 560-571.

Savas, J. N., Toyama, B. H., Xu, T., Yates, J. R., 3rd and Hetzer, M. W. (2012).Extremely long-lived nuclear pore proteins in the rat brain. Science 335, 942.

SCHOOLEY, A., VOLLMER, B. AND ANTONIN, W. (2012). Building a nuclear envelope atthe end of mitosis: coordinating membrane reorganization, nuclear porecomplex assembly, and chromatin de-condensation. Chromosoma 121, 539-554.

Segref, A., Sharma, K., Doye, V., Hellwig, A., Huber, J., Luhrmann, R. andHurt, E. (1997). Mex67p, a novel factor for nuclear mRNA export, binds to bothpoly(A)+ RNA and nuclear pores. EMBO J. 16, 3256-3271.

Simon, D. N. and Rout, M. P. (2014). Cancer and the nuclear pore complex. Adv.Exp. Med. Biol. 773, 285-307.

Siniossoglou, S., Wimmer, C., Rieger, M., Doye, V., Tekotte, H., Weise, C.,Emig, S., Segref, A. and Hurt, E. C. (1996). A novel complex of nucleoporins,

CELL SCIENCE AT A GLANCE Journal of Cell Science (2015) 128, 423–429 doi:10.1242/jcs.083246

428

Jour

nal o

f Cel

l Sci

ence

which includes Sec13p and a Sec13p homolog, is essential for normal nuclearpores. Cell 84, 265-275.

Stewart, M. (2007a). Ratcheting mRNA out of the nucleus. Mol. Cell 25, 327-330.

Stewart, M. (2007b). Molecular mechanism of the nuclear protein import cycle.Nat. Rev. Mol. Cell Biol. 8, 195-208.

Stewart, M. (2010). Nuclear export of mRNA. Trends Biochem. Sci. 35, 609-617.

Stoffler, D., Feja, B., Fahrenkrog, B., Walz, J., Typke, D. and Aebi, U. (2003).Cryo-electron tomography provides novel insights into nuclear pore architecture:implications for nucleocytoplasmic transport. J. Mol. Biol. 328, 119-130.

Stuwe, T., Lin, D. H., Collins, L. N., Hurt, E. and Hoelz, A. (2014). Evidence foran evolutionary relationship between the large adaptor nucleoporin Nup192 andkaryopherins. Proc. Natl. Acad. Sci. USA 111, 2530-2535.

Terry, L. J. and Wente, S. R. (2009). Flexible gates: dynamic topologies andfunctions for FG nucleoporins in nucleocytoplasmic transport. Eukaryot. Cell 8,1814-1827.

Texari, L., Dieppois, G., Vinciguerra, P., Contreras, M. P., Groner, A., Letourneau,A. and Stutz, F. (2013). The nuclear pore regulates GAL1 gene transcription bycontrolling the localization of the SUMO protease Ulp1. Mol. Cell 51, 807-818.

Toyama, B. H., Savas, J. N., Park, S. K., Harris, M. S., Ingolia, N. T., Yates,J. R., III and Hetzer, M. W. (2013). Identification of long-lived proteins revealsexceptional stability of essential cellular structures. Cell 154, 971-982.

Tran, E. J., Zhou, Y., Corbett, A. H. and Wente, S. R. (2007). The DEAD-boxprotein Dbp5 controls mRNA export by triggering specific RNA:proteinremodeling events. Mol. Cell 28, 850-859.

Tschochner, H. and Hurt, E. (2003). Pre-ribosomes on the road from thenucleolus to the cytoplasm. Trends Cell Biol. 13, 255-263.

Van de Vosse, D. W., Wan, Y., Lapetina, D. L., Chen, W.-M., Chiang,J.-H., Aitchison, J. D. and Wozniak, R. W. (2013). A role for thenucleoporin Nup170p in chromatin structure and gene silencing. Cell 152,969-983.

Vollmer, B. and Antonin, W. (2014). The diverse roles of the Nup93/Nic96complex proteins – structural scaffolds of the nuclear pore complex withadditional cellular functions. Biol. Chem. 395, 515-528.

Walther, T. C., Alves, A., Pickersgill, H., Loıodice, I., Hetzer, M., Galy, V.,Hulsmann, B. B., Kocher, T., Wilm, M., Allen, T. et al. (2003). The conservedNup107-160 complex is critical for nuclear pore complex assembly. Cell 113,195-206.

Weirich, C. S., Erzberger, J. P., Flick, J. S., Berger, J. M., Thorner, J. and Weis,K. (2006). Activation of the DExD/H-box protein Dbp5 by the nuclear-poreprotein Gle1 and its coactivator InsP6 is required for mRNA export. Nat. CellBiol. 8, 668-676.

Weis, K. (2003). Regulating access to the genome: nucleocytoplasmic transportthroughout the cell cycle. Cell 112, 441-451.

Yamada, J., Phillips, J. L., Patel, S., Goldfien, G., Calestagne-Morelli, A.,Huang, H., Reza, R., Acheson, J., Krishnan, V. V., Newsam, S. et al. (2010). Abimodal distribution of two distinct categories of intrinsically disordered structureswith separate functions in FG nucleoporins. Mol. Cell. Proteomics 9, 2205-2224.

Yang, W., Gelles, J. and Musser, S. M. (2004). Imaging of single-moleculetranslocation through nuclear pore complexes. Proc. Natl. Acad. Sci. USA 101,12887-12892.

Yavuz, S., Santarella-Mellwig, R., Koch, B., Jaedicke, A., Mattaj, I. W. andAntonin, W. (2010). NLS-mediated NPC functions of the nucleoporin Pom121.FEBS Lett. 584, 3292-3298.

Zemp, I. and Kutay, U. (2007). Nuclear export and cytoplasmic maturation ofribosomal subunits. FEBS Lett. 581, 2783-2793.

Zilman, A., Di Talia, S., Jovanovic-Talisman, T., Chait, B. T., Rout, M. P. andMagnasco, M. O. (2010). Enhancement of transport selectivity through nano-channels by non-specific competition. PLOS Comput. Biol. 6, e1000804.

Zuccolo, M., Alves, A., Galy, V., Bolhy, S., Formstecher, E., Racine, V.,Sibarita, J.-B., Fukagawa, T., Shiekhattar, R., Yen, T. et al. (2007). The humanNup107-160 nuclear pore subcomplex contributes to proper kinetochorefunctions. EMBO J. 26, 1853-1864.

CELL SCIENCE AT A GLANCE Journal of Cell Science (2015) 128, 423–429 doi:10.1242/jcs.083246

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