scholarly journals Importins and Exportins Regulating Allergic Immune Responses

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Ankita Aggarwal ◽  
Devendra K. Agrawal
Keyword(s):  
Transcription Factors ◽  
Nuclear Export ◽  
Molecular Mechanisms ◽  
Allergic Diseases ◽  
Nuclear Pore ◽  
Nuclear Pore Complexes ◽  
Immune Modulators ◽  
Nuclear Localization Signals ◽  
Intracellular Signals ◽  
Pore Complexes

Nucleocytoplasmic shuttling of macromolecules is a well-controlled process involving importins and exportins. These karyopherins recognize and bind to receptor-mediated intracellular signals through specific signal sequences that are present on cargo proteins and transport into and out of the nucleus through nuclear pore complexes. Nuclear localization signals (NLS) present on cargo molecules to be imported while nuclear export signals (NES) on the molecules to be exported are recognized by importins and exportins, respectively. The classical NLS are found on many transcription factors and molecules that are involved in the pathogenesis of allergic diseases. In addition, several immune modulators, including corticosteroids and vitamin D, elicit their cellular responses by regulating the expression and activity of importin molecules. In this review article, we provide a comprehensive list of importin and exportin molecules and their specific cargo that shuttled between cytoplasm and the nucleus. We also critically review the role and regulation of specific importin and exportin involved in the transport of activated transcription factors in allergic diseases, the underlying molecular mechanisms, and the potential target sites for developing better therapeutic approaches.

Nuclear localization signals for four distinct karyopherin-β nuclear import systems

2015 ◽  
Vol 468 (3) ◽  
pp. 353-362 ◽  
Author(s):  
Michael Soniat ◽  
Yuh Min Chook
Keyword(s):  
Nuclear Localization ◽  
Nuclear Export ◽  
Nuclear Pore ◽  
Nuclear Pore Complexes ◽  
Paper Briefly ◽  
Nuclear Localization Signals ◽  
Importin Α ◽  
Pore Complexes ◽  
First Time ◽  
Transport Of Macromolecules

The Karyopherin-β family of proteins mediates nuclear transport of macromolecules. Nuclear versus cytoplasmic localization of proteins is often suggested by the presence of NLSs (nuclear localization signals) or NESs (nuclear export signals). Import-Karyopherin-βs or Importins bind to NLSs in their protein cargos to transport them through nuclear pore complexes into the nucleus. Until recently, only two classes of NLS had been biochemically and structurally characterized: the classical NLS, which is recognized by the Importin-α/β heterodimer and the PY-NLS (proline–tyrosine NLS), which is recognized by Karyopherin-β2 or Transportin-1. Structures of two other Karyopherin-βs, Kap121 and Transportin-SR2, in complex with their respective cargos were reported for the first time recently, revealing two new distinct classes of NLSs. The present paper briefly describes the classical NLS, reviews recent literature on the PY-NLS and provides in-depth reviews of the two newly discovered classes of NLSs that bind Kap121p and Transportin-SR respectively.

scholarly journals The nuclear pore complex: mediator of translocation between nucleus and cytoplasm

2000 ◽  
Vol 113 (10) ◽  
pp. 1651-1659 ◽  
Author(s):  
T.D. Allen ◽  
J.M. Cronshaw ◽  
S. Bagley ◽  
E. Kiseleva ◽  
M.W. Goldberg
Keyword(s):  
Nuclear Export ◽  
Mammalian Cells ◽  
Complex Structure ◽  
Nuclear Pore ◽  
Nuclear Pore Complexes ◽  
Complete Breakdown ◽  
Import And Export ◽  
Complex Structural ◽  
Pore Complexes ◽  
Giant Nuclei

The enclosure of nuclear contents in eukaryotes means that cells require sites in the boundary that mediate exchange of material between nucleus and cytoplasm. These sites, termed nuclear pore complexes (NPCs), number 100–200 in yeast, a few thousand in mammalian cells and approximately 50 million in the giant nuclei of amphibian oocytes. NPCs are large (125 MDa) macromolecular complexes that comprise 50–100 different proteins in vertebrates. In spite of their size and complex structure, NPCs undergo complete breakdown and reformation at cell division. Transport through NPCs can be rapid (estimated at several hundred molecules/pore/second) and accommodates both passive diffusion of relatively small molecules, and active transport of complexes up to several megadaltons in molecular mass. Each pore can facilitate both import and export. The two processes apparently involve multiple pathways for different cargoes, and their transport signals, transport receptors and adapters, and the molecules (and their regulators) that underpin the transport mechanisms. Over the past few years there has been an increasing interest in the pore complex: structural studies have been followed by elucidation of the biochemical aspects of nuclear import, and subsequent investigations into nuclear export. The current challenge is to understand the interactions between the structural elements of the pore complex and the mechanisms that drive the physical processes of translocation through it.

scholarly journals RanBP2/Nup358 Provides a Major Binding Site for NXF1-p15 Dimers at the Nuclear Pore Complex and Functions in Nuclear mRNA Export

2004 ◽  
Vol 24 (3) ◽  
pp. 1155-1167 ◽  
Author(s):  
Daniel Forler ◽  
Gwénaël Rabut ◽  
Francesca D. Ciccarelli ◽  
Andrea Herold ◽  
Thomas Köcher ◽  
...  
Keyword(s):  
Binding Site ◽  
Nuclear Export ◽  
Mrna Export ◽  
Stable Complex ◽  
Nuclear Pore ◽  
Nuclear Pore Complexes ◽  
Cytoplasmic Filaments ◽  
Nuclear Levels ◽  
Pore Complexes

ABSTRACT Metazoan NXF1-p15 heterodimers promote the nuclear export of bulk mRNA across nuclear pore complexes (NPCs). In vitro, NXF1-p15 forms a stable complex with the nucleoporin RanBP2/Nup358, a component of the cytoplasmic filaments of the NPC, suggesting a role for this nucleoporin in mRNA export. We show that depletion of RanBP2 from Drosophila cells inhibits proliferation and mRNA export. Concomitantly, the localization of NXF1 at the NPC is strongly reduced and a significant fraction of this normally nuclear protein is detected in the cytoplasm. Under the same conditions, the steady-state subcellular localization of other nuclear or cytoplasmic proteins and CRM1-mediated protein export are not detectably affected, indicating that the release of NXF1 into the cytoplasm and the inhibition of mRNA export are not due to a general defect in NPC function. The specific role of RanBP2 in the recruitment of NXF1 to the NPC is highlighted by the observation that depletion of CAN/Nup214 also inhibits cell proliferation and mRNA export but does not affect NXF1 localization. Our results indicate that RanBP2 provides a major binding site for NXF1 at the cytoplasmic filaments of the NPC, thereby restricting its diffusion in the cytoplasm after NPC translocation. In RanBP2-depleted cells, NXF1 diffuses freely through the cytoplasm. Consequently, the nuclear levels of the protein decrease and export of bulk mRNA is impaired.

scholarly journals Steady-State Nuclear Localization of Exportin-t Involves RanGTP Binding and Two Distinct Nuclear Pore Complex Interaction Domains

2002 ◽  
Vol 22 (16) ◽  
pp. 5708-5720 ◽  
Author(s):  
Scott Kuersten ◽  
Gert-Jan Arts ◽  
Tobias C. Walther ◽  
Ludwig Englmeier ◽  
Iain W. Mattaj
Keyword(s):  
Steady State ◽  
Nuclear Export ◽  
Nuclear Pore ◽  
Nuclear Pore Complexes ◽  
Dependent Manner ◽  
C Terminus ◽  
Transport Cycle ◽  
Interaction Domains ◽  
Pore Complexes

ABSTRACT Vertebrate tRNA export receptor exportin-t (Xpo-t) binds to RanGTP and mature tRNAs cooperatively to form a nuclear export complex. Xpo-t shuttles bidirectionally through nuclear pore complexes (NPCs) but is mainly nuclear at steady state. The steady-state distribution of Xpo-t is shown to depend on its interaction with RanGTP. Two distinct Xpo-t NPC interaction domains that bind differentially to peripherally localized nucleoporins in vitro are identified. The N terminus binds to both Nup153 and RanBP2/Nup358 in a RanGTP-dependent manner, while the C terminus binds to CAN/Nup214 independently of Ran. We propose that these interactions increase the concentration of tRNA export complexes and of empty Xpo-t in the vicinity of NPCs and thus increase the efficiency of the Xpo-t transport cycle.

scholarly journals Altered RNA processing and export lead to retention of mRNAs near transcription sites and nuclear pore complexes or within the nucleolus

2016 ◽  
Vol 27 (17) ◽  
pp. 2742-2756 ◽  
Author(s):  
Biplab Paul ◽  
Ben Montpetit
Keyword(s):  
Single Molecule ◽  
Rna Processing ◽  
Nuclear Export ◽  
Essential Gene ◽  
Nucleocytoplasmic Transport ◽  
Nuclear Pore ◽  
Nuclear Pore Complexes ◽  
Eukaryotic Gene ◽  
Transcription Sites ◽  
Pore Complexes

Many protein factors are required for mRNA biogenesis and nuclear export, which are central to the eukaryotic gene expression program. It is unclear, however, whether all factors have been identified. Here we report on a screen of >1000 essential gene mutants in Saccharomyces cerevisiae for defects in mRNA processing and export, identifying 26 mutants with defects in this process. Single-molecule FISH data showed that the majority of these mutants accumulated mRNA within specific regions of the nucleus, which included 1) mRNAs within the nucleolus when nucleocytoplasmic transport, rRNA biogenesis, or RNA processing and surveillance was disrupted, 2) the buildup of mRNAs near transcription sites in 3′-end processing and chromosome segregation mutants, and 3) transcripts being enriched near nuclear pore complexes when components of the mRNA export machinery were mutated. These data show that alterations to various nuclear processes lead to the retention of mRNAs at discrete locations within the nucleus.

scholarly journals Distinct Basket Nucleoporins roles in Nuclear Pore Function and Gene Expression: Tpr is an integral component of the TREX-2 mRNA export pathway

2019 ◽  
Author(s):  
Vasilisa Aksenova ◽  
Hang Noh Lee ◽  
Alexandra Smith ◽  
Shane Chen ◽  
Prasanna Bhat ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nuclear Export ◽  
Protein Modification ◽  
Mrna Export ◽  
Nuclear Pore ◽  
Nuclear Pore Complexes ◽  
Nucleocytoplasmic Trafficking ◽  
Pore Complexes ◽  
Slow Turnover

AbstractNuclear pore complexes (NPCs) are important for many processes beyond nucleocytoplasmic trafficking, including protein modification, chromatin remodeling, transcription, mRNA processing and mRNA export. The multi-faceted nature of NPCs and the slow turnover of their components has made it difficult to understand the role of basket nucleoporins (Nup153, Nup50 and Tpr) in these diverse processes. To address this question, we used anAuxin-InducedDegron (AID) system to distinguish roles of basket nucleoporins: Loss of individual nucleoporins caused distinct alteration in patterns of nucleocytoplasmic trafficking and gene expression. Importantly, Tpr elimination caused rapid and pronounced changes in transcriptomic profiles within two hours of auxin addition. These changes were dissimilar to shifts observed after loss of Nup153 or Nup50, but closely related to changes after depletion of mRNA export receptor NXF1 or the GANP subunit of the TRanscription-EXport-2 (TREX-2) mRNA export complex. Moreover, GANP association to NPCs was specifically disrupted upon TPR depletion. Together, our findings demonstrate a unique and pivotal role of Tpr in regulating gene expression through GANP- and/or NXF1-dependent mRNA nuclear export.

scholarly journals Origin of the nuclear proteome on the basis of pre-existing nuclear localization signals in prokaryotic proteins

2020 ◽  
Author(s):  
Olga M. Lisitsyna ◽  
Margarita A. Kurnaeva ◽  
Eugene A. Arifulin ◽  
Maria Y. Shubina ◽  
Yana R. Musinova ◽  
...  
Keyword(s):  
Nuclear Localization ◽  
Protein Import ◽  
Eukaryotic Cell ◽  
Nuclear Pore ◽  
Nuclear Pore Complexes ◽  
Nuclear Localization Signals ◽  
Binding Domains ◽  
Nuclear Proteome ◽  
Pore Complexes ◽  
Open Question

AbstractThe origin of the selective nuclear protein import machinery, which consists of nuclear pore complexes and adaptor molecules interacting with the nuclear localization signals (NLSs) of cargo molecules, was one of the most important events in the evolution of the eukaryotic cell. How the proteins were selected for import into the forming nuclei remains an open question. Here, we demonstrate that functional NLSs may be integrated inside nucleotide-binding domains of both eukaryotic and prokaryotic proteins and may co-evolve with these domains. We propose that the pre-existence of NLSs inside prokaryotic proteins dictated, at least partially, the nuclear proteome composition.

scholarly journals Nuclear Pore Complex Acetylation Regulates mRNA Export and Cell Cycle Commitment in Budding Yeast

2021 ◽  
Author(s):  
Mercè Gomar-Alba ◽  
Vasilisa Pozharskaia ◽  
Celia Schaal ◽  
Arun Kumar ◽  
Basile Jacquel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nuclear Export ◽  
Mrna Export ◽  
Cell Types ◽  
Nuclear Pore ◽  
Specific Cell ◽  
Nuclear Pore Complexes ◽  
Daughter Cells ◽  
Associated Proteins ◽  
Pore Complexes

AbstractNuclear pore complexes (NPCs) mediate communication between the nucleus and the cytoplasm and regulate gene expression by interacting with transcription and mRNA export factors. Lysine acetyl-transferases (KATs) promote transcription through acetylation of chromatin-associated proteins. We find that Esa1, the KAT subunit of the yeast NuA4 complex, also acetylates the nuclear pore basket component Nup60 to promote mRNA export. Acetylation of Nup60 recruits mRNA export factors to the nuclear basket, including the scaffolding subunit of the Transcription and Export 2 (TREX-2) complex, Sac3. Esa1-dependent nuclear export of mRNAs promotes entry into S phase, and is inhibited by the Hos3 deacetylase in G1 daughter cells to restrain their premature commitment to a new cell division cycle. This mechanism also inhibits expression of the nutrient-regulated GAL1 gene specifically in daughter cells. These results reveal how acetylation contributes to the functional plasticity of NPCs in specific cell types, and demonstrate how the evolutionarily conserved NuA4 complex regulates gene expression dually at the level of transcription and mRNA export, by modifying the nucleoplasmic entrance to nuclear pores.

scholarly journals Dissection of the NUP107 nuclear pore subcomplex reveals a novel interaction with spindle assembly checkpoint protein MAD1 in Caenorhabditis elegans

2012 ◽  
Vol 23 (5) ◽  
pp. 930-944 ◽  
Author(s):  
Eduardo Ródenas ◽  
Cristina González-Aguilera ◽  
Cristina Ayuso ◽  
Peter Askjaer
Keyword(s):  
Caenorhabditis Elegans ◽  
Nuclear Envelope ◽  
Molecular Mechanisms ◽  
Spindle Assembly Checkpoint ◽  
Protein Import ◽  
Spindle Assembly ◽  
Nucleocytoplasmic Transport ◽  
Nuclear Pore ◽  
Nuclear Pore Complexes ◽  
Pore Complexes

Nuclear pore complexes consist of several subcomplexes. The NUP107 complex is important for nucleocytoplasmic transport, nuclear envelope assembly, and kinetochore function. However, the underlying molecular mechanisms and the roles of individual complex members remain elusive. We report the first description of a genetic disruption of NUP107 in a metazoan. Caenorhabditis elegans NUP107/npp-5 mutants display temperature-dependent lethality. Surprisingly, NPP-5 is dispensable for incorporation of most nucleoporins into nuclear pores and for nuclear protein import. In contrast, NPP-5 is essential for proper kinetochore localization of NUP133/NPP-15, another NUP107 complex member, whereas recruitment of NUP96/NPP-10C and ELYS/MEL-28 is NPP-5 independent. We found that kinetochore protein NUF2/HIM-10 and Aurora B/AIR-2 kinase are less abundant on mitotic chromatin upon NPP-5 depletion. npp-5 mutants are hypersensitive to anoxia, suggesting that the spindle assembly checkpoint (SAC) is compromised. Indeed, NPP-5 interacts genetically and physically with SAC protein MAD1/MDF-1, whose nuclear envelope accumulation requires NPP-5. Thus our results strengthen the emerging connection between nuclear pore proteins and chromosome segregation.

scholarly journals Leukemia-Associated Nup214 Fusion Proteins Disturb the XPO1-Mediated Nuclear-Cytoplasmic Transport Pathway and Thereby the NF-κB Signaling Pathway

2016 ◽  
Vol 36 (13) ◽  
pp. 1820-1835 ◽  
Author(s):  
Shoko Saito ◽  
Sadik Cigdem ◽  
Mitsuru Okuwaki ◽  
Kyosuke Nagata
Keyword(s):  
Signaling Pathway ◽  
Nuclear Export ◽  
Fusion Proteins ◽  
Nuclear Transport ◽  
Nuclear Pore ◽  
Nuclear Pore Complexes ◽  
Transport Pathway ◽  
Cytoplasmic Transport ◽  
Transport Receptors ◽  
Pore Complexes

Nuclear-cytoplasmic transport through nuclear pore complexes is mediated by nuclear transport receptors. Previous reports have suggested that aberrant nuclear-cytoplasmic transport due to mutations or overexpression of nuclear pore complexes and nuclear transport receptors is closely linked to diseases. Nup214, a component of nuclear pore complexes, has been found as chimeric fusion proteins in leukemia. Among various Nup214 fusion proteins, SET-Nup214 and DEK-Nup214 have been shown to be engaged in tumorigenesis, but their oncogenic mechanisms remain unclear. In this study, we examined the functions of the Nup214 fusion proteins by focusing on their effects on nuclear-cytoplasmic transport. We found that SET-Nup214 and DEK-Nup214 interact with exportin-1 (XPO1)/CRM1 and nuclear RNA export factor 1 (NXF1)/TAP, which mediate leucine-rich nuclear export signal (NES)-dependent protein export and mRNA export, respectively. SET-Nup214 and DEK-Nup214 decreased the XPO1-mediated nuclear export of NES proteins such as cyclin B and proteins involved in the NF-κB signaling pathway by tethering XPO1 onto nuclear dots where Nup214 fusion proteins are localized. We also demonstrated that SET-Nup214 and DEK-Nup214 expression inhibited NF-κB-mediated transcription by abnormal tethering of the complex containing p65 and its inhibitor, IκB, in the nucleus. These results suggest that SET-Nup214 and DEK-Nup214 perturb the regulation of gene expression through alteration of the nuclear-cytoplasmic transport system.

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