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  1. Artikel ; Online: Dynamics of nuclear export of pre-ribosomal subunits revealed by high-speed single-molecule microscopy in live cells.

    Junod, Samuel L / Tingey, Mark / Kelich, Joseph M / Goryaynov, Alexander / Herbine, Karl / Yang, Weidong

    iScience

    2023  Band 26, Heft 8, Seite(n) 107445

    Abstract: We present a study on the nuclear export efficiency and time of pre-ribosomal subunits in live mammalian cells, using high-speed single-molecule tracking and single-molecule fluorescence resonance energy transfer techniques. Our findings reveal that pre- ... ...

    Abstract We present a study on the nuclear export efficiency and time of pre-ribosomal subunits in live mammalian cells, using high-speed single-molecule tracking and single-molecule fluorescence resonance energy transfer techniques. Our findings reveal that pre-ribosomal particles exhibit significantly higher nuclear export efficiency compared to other large cargos like mRNAs, with around two-thirds of interactions between the pre-60S or pre-40S and the nuclear pore complexes (NPCs) resulting in successful export to the cytoplasm. We also demonstrate that nuclear transport receptor (NTR) chromosomal maintenance 1 (CRM1) plays a crucial role in nuclear export efficiency, with pre-60S and pre-40S particle export efficiency decreasing by 11-17-fold when CRM1 is inhibited. Our results suggest that multiple copies of CRM1 work cooperatively to chaperone pre-ribosomal subunits through the NPC, thus increasing export efficiency and decreasing export time. Significantly, this cooperative NTR mechanism extends beyond pre-ribosomal subunits, as evidenced by the enhanced nucleocytoplasmic transport of proteins.
    Sprache Englisch
    Erscheinungsdatum 2023-07-21
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ISSN 2589-0042
    ISSN (online) 2589-0042
    DOI 10.1016/j.isci.2023.107445
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Structural basis for DNA proofreading.

    Buchel, Gina / Nayak, Ashok R / Herbine, Karl / Sarfallah, Azadeh / Sokolova, Viktoriia O / Zamudio-Ochoa, Angelica / Temiakov, Dmitry

    Nature communications

    2023  Band 14, Heft 1, Seite(n) 8501

    Abstract: DNA polymerase (DNAP) can correct errors in DNA during replication by proofreading, a process critical for cell viability. However, the mechanism by which an erroneously incorporated base translocates from the polymerase to the exonuclease site and the ... ...

    Abstract DNA polymerase (DNAP) can correct errors in DNA during replication by proofreading, a process critical for cell viability. However, the mechanism by which an erroneously incorporated base translocates from the polymerase to the exonuclease site and the corrected DNA terminus returns has remained elusive. Here, we present an ensemble of nine high-resolution structures representing human mitochondrial DNA polymerase Gamma, Polγ, captured during consecutive proofreading steps. The structures reveal key events, including mismatched base recognition, its dissociation from the polymerase site, forward translocation of DNAP, alterations in DNA trajectory, repositioning and refolding of elements for primer separation, DNAP backtracking, and displacement of the mismatched base into the exonuclease site. Altogether, our findings suggest a conserved 'bolt-action' mechanism of proofreading based on iterative cycles of DNAP translocation without dissociation from the DNA, facilitating primer transfer between catalytic sites. Functional assays and mutagenesis corroborate this mechanism, connecting pathogenic mutations to crucial structural elements in proofreading steps.
    Mesh-Begriff(e) Humans ; DNA Replication/genetics ; DNA-Directed DNA Polymerase/metabolism ; DNA/genetics ; DNA/chemistry ; Exonucleases/metabolism
    Chemische Substanzen dinitroaminophenol (J04VBD97F1) ; DNA-Directed DNA Polymerase (EC 2.7.7.7) ; DNA (9007-49-2) ; Exonucleases (EC 3.1.-)
    Sprache Englisch
    Erscheinungsdatum 2023-12-27
    Erscheinungsland England
    Dokumenttyp Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-023-44198-8
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: Cell-Intrinsic Wnt4 Influences Conventional Dendritic Cell Fate Determination to Suppress Type 2 Immunity.

    Hung, Li-Yin / Johnson, John L / Ji, Yingbiao / Christian, David A / Herbine, Karl R / Pastore, Christopher F / Herbert, De'Broski R

    Journal of immunology (Baltimore, Md. : 1950)

    2019  Band 203, Heft 2, Seite(n) 511–519

    Abstract: Whether conventional dendritic cells (cDC) acquire subset identity under direction of Wnt family glycoproteins is unknown. We demonstrate that Wnt4, a β-catenin-independent Wnt ligand, is produced by both hematopoietic and nonhematopoietic cells and is ... ...

    Abstract Whether conventional dendritic cells (cDC) acquire subset identity under direction of Wnt family glycoproteins is unknown. We demonstrate that Wnt4, a β-catenin-independent Wnt ligand, is produced by both hematopoietic and nonhematopoietic cells and is both necessary and sufficient for preconventional DC1/cDC1 maintenance. Whereas bone marrow cDC precursors undergo phosphoJNK/c-Jun activation upon Wnt4 treatment, loss of cDC Wnt4 in CD11c
    Mesh-Begriff(e) Animals ; Antigens, CD/immunology ; CD11c Antigen/immunology ; CD24 Antigen/immunology ; Cell Differentiation/immunology ; Dendritic Cells/immunology ; Flow Cytometry/methods ; Immunity, Innate/immunology ; Integrin alpha Chains/immunology ; Lymphocytes/immunology ; Mice ; Signal Transduction/immunology ; Wnt4 Protein/immunology ; beta Catenin/immunology
    Chemische Substanzen Antigens, CD ; CD11c Antigen ; CD24 Antigen ; Integrin alpha Chains ; Wnt4 Protein ; Wnt4 protein, mouse ; alpha E integrins ; beta Catenin
    Sprache Englisch
    Erscheinungsdatum 2019-06-07
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 3056-9
    ISSN 1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
    ISSN (online) 1550-6606
    ISSN 0022-1767 ; 1048-3233 ; 1047-7381
    DOI 10.4049/jimmunol.1900363
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel ; Online: LINGO3 regulates mucosal tissue regeneration and promotes TFF2 dependent recovery from colitis.

    Zullo, Kelly M / Douglas, Bonnie / Maloney, Nicole M / Ji, Yingbiao / Wei, Yun / Herbine, Karl / Cohen, Rachel / Pastore, Christopher / Cramer, Zvi / Wang, Xin / Wei, Wenjie / Somsouk, Ma / Hung, Li Yin / Lengner, Christopher / Kohanski, Michael H / Cohen, Noam A / Herbert, De'Broski R

    Scandinavian journal of gastroenterology

    2021  Band 56, Heft 7, Seite(n) 791–805

    Abstract: Aim: ...

    Abstract Aim:
    Mesh-Begriff(e) Colitis ; Humans ; Intestinal Mucosa ; Organoids ; Trefoil Factor-2 ; Wound Healing
    Chemische Substanzen TFF2 protein, human ; Trefoil Factor-2
    Sprache Englisch
    Erscheinungsdatum 2021-05-03
    Erscheinungsland England
    Dokumenttyp Journal Article
    ZDB-ID 82042-8
    ISSN 1502-7708 ; 0036-5521
    ISSN (online) 1502-7708
    ISSN 0036-5521
    DOI 10.1080/00365521.2021.1917650
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel ; Online: TFF3 interacts with LINGO2 to regulate EGFR activation for protection against colitis and gastrointestinal helminths.

    Belle, Nicole Maloney / Ji, Yingbiao / Herbine, Karl / Wei, Yun / Park, JoonHyung / Zullo, Kelly / Hung, Li-Yin / Srivatsa, Sriram / Young, Tanner / Oniskey, Taylor / Pastore, Christopher / Nieves, Wildaliz / Somsouk, Ma / Herbert, De'Broski R

    Nature communications

    2019  Band 10, Heft 1, Seite(n) 4408

    Abstract: Intestinal epithelial cells (IEC) have important functions in nutrient absorption, barrier integrity, regeneration, pathogen-sensing, and mucus secretion. Goblet cells are a specialized cell type of IEC that secrete Trefoil factor 3 (TFF3) to regulate ... ...

    Abstract Intestinal epithelial cells (IEC) have important functions in nutrient absorption, barrier integrity, regeneration, pathogen-sensing, and mucus secretion. Goblet cells are a specialized cell type of IEC that secrete Trefoil factor 3 (TFF3) to regulate mucus viscosity and wound healing, but whether TFF3-responsiveness requires a receptor is unclear. Here, we show that leucine rich repeat receptor and nogo-interacting protein 2 (LINGO2) is essential for TFF3-mediated functions. LINGO2 immunoprecipitates with TFF3, co-localizes with TFF3 on the cell membrane of IEC, and allows TFF3 to block apoptosis. We further show that TFF3-LINGO2 interactions disrupt EGFR-LINGO2 complexes resulting in enhanced EGFR signaling. Excessive basal EGFR activation in Lingo2 deficient mice increases disease severity during colitis and augments immunity against helminth infection. Conversely, TFF3 deficiency reduces helminth immunity. Thus, TFF3-LINGO2 interactions de-repress inhibitory LINGO2-EGFR complexes, allowing TFF3 to drive wound healing and immunity.
    Mesh-Begriff(e) Animals ; Cell Line, Tumor ; Colitis/chemically induced ; Colitis/immunology ; Colitis/metabolism ; Dextran Sulfate ; ErbB Receptors/genetics ; ErbB Receptors/immunology ; ErbB Receptors/metabolism ; Goblet Cells/immunology ; Goblet Cells/metabolism ; Goblet Cells/parasitology ; HEK293 Cells ; Helminthiasis/immunology ; Helminthiasis/metabolism ; Helminthiasis/parasitology ; Helminths/immunology ; Helminths/physiology ; Humans ; Intestinal Mucosa/immunology ; Intestinal Mucosa/metabolism ; Intestinal Mucosa/parasitology ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Mice, Inbred C57BL ; Nerve Tissue Proteins/genetics ; Nerve Tissue Proteins/immunology ; Nerve Tissue Proteins/metabolism ; Organophosphonates ; Trefoil Factor-3/genetics ; Trefoil Factor-3/immunology ; Trefoil Factor-3/metabolism ; U937 Cells
    Chemische Substanzen Lingo2 protein, mouse ; Membrane Proteins ; Nerve Tissue Proteins ; Organophosphonates ; Tff3 protein, mouse ; Trefoil Factor-3 ; (2-(dimethylamino)ethyl)phosphonic acid (14596-56-6) ; Dextran Sulfate (9042-14-2) ; EGFR protein, mouse (EC 2.7.10.1) ; ErbB Receptors (EC 2.7.10.1)
    Sprache Englisch
    Erscheinungsdatum 2019-09-27
    Erscheinungsland England
    Dokumenttyp Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-019-12315-1
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  6. Artikel ; Online: Cellular context of IL-33 expression dictates impact on anti-helminth immunity.

    Hung, Li-Yin / Tanaka, Yukinori / Herbine, Karl / Pastore, Christopher / Singh, Brenal / Ferguson, Annabel / Vora, Nisha / Douglas, Bonnie / Zullo, Kelly / Behrens, Edward M / Li Hui Tan, Tiffany / Kohanski, Michael A / Bryce, Paul / Lin, Cailu / Kambayashi, Taku / Reed, Danielle R / Brown, Breann L / Cohen, Noam A / Herbert, De'Broski R

    Science immunology

    2020  Band 5, Heft 53

    Abstract: Interleukin-33 (IL-33) is a pleiotropic cytokine that can promote type 2 inflammation but also drives immunoregulation through ... ...

    Abstract Interleukin-33 (IL-33) is a pleiotropic cytokine that can promote type 2 inflammation but also drives immunoregulation through Foxp3
    Mesh-Begriff(e) Animals ; Cell Membrane/metabolism ; Chronic Disease ; Dendritic Cells/immunology ; Dendritic Cells/metabolism ; Disease Models, Animal ; Female ; Humans ; Immune Tolerance ; Immunity, Innate ; Immunity, Mucosal ; Interleukin-33/analysis ; Interleukin-33/genetics ; Interleukin-33/metabolism ; Male ; Membrane Proteins/metabolism ; Mice ; Mice, Transgenic ; Nasal Mucosa/immunology ; Nasal Mucosa/pathology ; Nasal Polyps/immunology ; Nasal Polyps/pathology ; Nematospiroides dubius/immunology ; Nippostrongylus/immunology ; Rhinitis/immunology ; Rhinitis/pathology ; Sinusitis/immunology ; Sinusitis/pathology ; Strongylida Infections/immunology ; Strongylida Infections/parasitology ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/metabolism
    Chemische Substanzen IL33 protein, human ; Il33 protein, mouse ; Interleukin-33 ; Membrane Proteins ; Mpeg1 protein, mouse
    Sprache Englisch
    Erscheinungsdatum 2020-11-13
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 2470-9468
    ISSN (online) 2470-9468
    DOI 10.1126/sciimmunol.abc6259
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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