Nucleoporin Nup358 drives the differentiation of myeloid-biased multipotent progenitors by modulating HDAC3 nuclear translocation.

Nucleoporins, the components of nuclear pore complexes (NPCs), can play cell type- and tissue-specific functions. Yet, the physiological roles and mechanisms of action for most NPC components have not yet been established. We report that Nup358, a nucleoporin linked to several myeloid disorders, is required for the developmental progression of early myeloid progenitors.

Analysis of Nuclear Pore Complex Permeability in Mammalian Cells and Isolated Nuclei Using Fluorescent Dextrans.

In eukaryotic cells the nuclear envelope encloses the genome separating it from the rest of the cell. Nuclear pore complexes are large multi protein channels that perforate the nuclear envelope, connecting the nucleus and the cytoplasm. Besides controlling nucleocytoplasmic molecule exchange, nuclear pore complexes create a permeability barrier that defines the maximum size of molecules that can freely diffuse into the nucleus.

Loss of Nup210 results in muscle repair delays and age-associated alterations in muscle integrity.

Nuclear pore complexes, the channels connecting the nucleus with the cytoplasm, are built by multiple copies of ∼30 proteins called nucleoporins. Recent evidence has exposed that nucleoporins can play cell type-specific functions. Despite novel discoveries into the cellular functions of nucleoporins, their role in the regulation of mammalian tissue physiology remains mostly unexplored because of a limited number of nucleoporin mouse models.

Structure, Maintenance, and Regulation of Nuclear Pore Complexes: The Gatekeepers of the Eukaryotic Genome.

In eukaryotic cells, the genetic material is segregated inside the nucleus. This compartmentalization of the genome requires a transport system that allows cells to move molecules across the nuclear envelope, the membrane-based barrier that surrounds the chromosomes. Nuclear pore complexes (NPCs) are the central component of the nuclear transport machinery.

Nuclear pore complexes in development and tissue homeostasis.

Nuclear pore complexes are multiprotein channels that span the nuclear envelope, which connects the nucleus to the cytoplasm. In addition to their main role in the regulation of nucleocytoplasmic molecule exchange, it has become evident that nuclear pore complexes and their components also have multiple transport-independent functions. In recent years, an increasing number of studies have reported the involvement of nuclear pore complex components in embryogenesis, cell differentiation and tissue-specific processes.

Inhibition of Nuclear Pore Complex Formation Selectively Induces Cancer Cell Death.

Nuclear pore complexes (NPC) are the central mediators of nucleocytoplasmic transport. Increasing evidence shows that many cancer cells have increased numbers of NPCs and become addicted to the nuclear transport machinery. How reducing NPC numbers affects the physiology of normal and cancer cells and whether it could be exploited for cancer therapies has not been investigated.

Nuclear Pore Complexes Are Key Regulators of Oligodendrocyte Differentiation and Function.

Increasing evidence points to nuclear pore complexes as important regulators of cell fate and tissue homeostasis. A recent report by Liu et al. (2019) in this issue of Neuron uncovers that nucleoporin Seh1 is required for the expression of genes critical for oligodendrocyte differentiation and myelination.

Nuclear pore complex-mediated modulation of TCR signaling is required for naïve CD4 T cell homeostasis.

Nuclear pore complexes (NPCs) are channels connecting the nucleus with the cytoplasm. We report that loss of the tissue-specific NPC component Nup210 causes a severe deficit of naïve CD4 T cells. Nup210-deficient CD4 T lymphocytes develop normally but fail to survive in the periphery.

Nup62-mediated nuclear import of p63 in squamous cell carcinoma.

Nuclear pore complexes (NPCs) are multiprotein channels that bridge the nucleus with the cytoplasm and regulate all nucleo‐cytoplasmic traffic. NPCs are built by the repetition of ~30 different proteins known as nucleoporins (Nups). Accumulating evidence has revealed a diversity in NPC composition that is critical for cell‐specific functionality and fate determination.

Nuclear pore complexes as hubs for gene regulation.

Nuclear pore complexes (NPCs), the channels connecting the nucleus with the cytoplasm, are the largest protein structures of the nuclear envelope. In addition to their role in regulating nucleocytoplasmic transport, increasing evidence shows that these multiprotein structures play central roles in the regulation of gene activity. In light of recent discoveries, NPCs are emerging as scaffolds that mediate the regulation of specific gene sets at the nuclear periphery.

Toolbox of Fluorescent Probes for Parallel Imaging Reveals Uneven Location of Serine Proteases in Neutrophils.

Neutrophils, the front line defenders against infection, express four serine proteases (NSPs) that play roles in the control of cell-signaling pathways and defense against pathogens and whose imbalance leads to pathological conditions. Dissecting the roles of individual NSPs in humans is problematic because neutrophils are end-stage cells with a short half-life and minimal ongoing protein synthesis. To gain insight into the regulation of NSP activity we have generated a small-molecule chemical toolbox consisting of activity-based probes with different fluorophore-detecting groups with minimal wavelength overlap and highly selective natural and unnatural amino acid recognition sequences.

The roles of the nuclear pore complex in cellular dysfunction, aging and disease.

The study of the Nuclear Pore Complex (NPC), the proteins that compose it (nucleoporins), and the nucleocytoplasmic transport that it controls have revealed an unexpected layer to pathogenic disease onset and progression. Recent advances in the study of the regulation of NPC composition and function suggest that the precise control of this structure is necessary to prevent diseases from arising or progressing. Here we discuss the role of nucleoporins in a diverse set of diseases, many of which directly or indirectly increase in occurrence and severity as we age, and often shorten the human lifespan.

Nuclear pore complexes and regulation of gene expression.

Nuclear pore complexes (NPCs), are large multiprotein channels that penetrate the nuclear envelope connecting the nucleus to the cytoplasm. Accumulating evidence shows that besides their main role in regulating the exchange of molecules between these two compartments, NPCs and their components also play important transport-independent roles, including gene expression regulation, chromatin organization, DNA repair, RNA processing and quality control, and cell cycle control. Here, we will describe the recent findings about the role of these structures in the regulation of gene expression.

Linking Nucleoporins, Mitosis, and Colon Cancer.

Suppression of a nuclear pore protein Nup358/RanBP2 is linked to mitotic cell death, but the clinical relevance of this link is unknown. In a recent issue of Cell, Vecchione et al. (2016) show that in approximately 10% of BRAF-like colorectal cancer (CC) patients, Nup358/RanBP2 is critical for survival.

Nuclear pore complexes in the maintenance of genome integrity.

Maintaining genome integrity is crucial for successful organismal propagation and for cell and tissue homeostasis. Several processes contribute to safeguarding the genomic information of cells. These include accurate replication of genetic information, detection and repair of DNA damage, efficient segregation of chromosomes, protection of chromosome ends, and proper organization of genome architecture.

Nuclear pore complex composition: a new regulator of tissue-specific and developmental functions.

Nuclear pore complexes (NPCs) are multiprotein aqueous channels that penetrate the nuclear envelope connecting the nucleus and the cytoplasm. NPCs consist of multiple copies of roughly 30 different proteins known as nucleoporins (NUPs). Due to their essential role in controlling nucleocytoplasmic transport, NPCs have traditionally been considered as structures of ubiquitous composition.

A change in nuclear pore complex composition regulates cell differentiation.

Nuclear pore complexes (NPCs) are built from ∼30 different proteins called nucleoporins or Nups. Previous studies have shown that several Nups exhibit cell-type-specific expression and that mutations in NPC components result in tissue-specific diseases. Here we show that a specific change in NPC composition is required for both myogenic and neuronal differentiation.

Age-dependent deterioration of nuclear pore complexes causes a loss of nuclear integrity in postmitotic cells.

In dividing cells, nuclear pore complexes (NPCs) disassemble during mitosis and reassemble into the newly forming nuclei. However, the fate of nuclear pores in postmitotic cells is unknown. Here, we show that NPCs, unlike other nuclear structures, do not turn over in differentiated cells.

Structure, dynamics and function of nuclear pore complexes.

Nuclear pore complexes are large aqueous channels that penetrate the nuclear envelope, thereby connecting the nuclear interior with the cytoplasm. Until recently, these macromolecular complexes were viewed as static structures, the only function of which was to control the molecular trafficking between the two compartments. It has now become evident that this simplistic scenario is inaccurate and that nuclear pore complexes are highly dynamic multiprotein assemblies involved in diverse cellular processes ranging from the organization of the cytoskeleton to gene expression.

Adenovirus core protein pVII is translocated into the nucleus by multiple import receptor pathways.

Adenoviruses are nonenveloped viruses with an approximately 36-kb double-stranded DNA genome that replicate in the nucleus. Protein VII, an abundant structural component of the adenovirus core that is strongly associated with adenovirus DNA, is imported into the nucleus contemporaneously with the adenovirus genome shortly after virus infection and may promote DNA import. In this study, we evaluated whether protein VII uses specific receptor-mediated mechanisms for import into the nucleus.

Nuclear pores form de novo from both sides of the nuclear envelope.

Nuclear pore complexes are multiprotein channels that span the double lipid bilayer of the nuclear envelope. How new pores are inserted into the intact nuclear envelope of proliferating and differentiating eukaryotic cells is unknown. We found that the Nup107-160 complex was incorporated into assembly sites in the nuclear envelope from both the nucleoplasmic and the cytoplasmic sides.

Identification, characterization and subcellular localization of TcPDE1, a novel cAMP-specific phosphodiesterase from Trypanosoma cruzi.

Compartmentalization of cAMP phosphodiesterases plays a key role in the regulation of cAMP signalling in mammals. In the present paper, we report the characterization and subcellular localization of TcPDE1, the first cAMP-specific phosphodiesterase to be identified from Trypanosoma cruzi. TcPDE1 is part of a small gene family and encodes a 929-amino-acid protein that can complement a heat-shock-sensitive yeast mutant deficient in phospho-diesterase genes.