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Most read article(s)

  • Decreasing pdzd8-mediated mito–ER contacts improves organismal fitness and mitigates Aβ<sub>42</sub> toxicity
    Open Access
    Decreasing pdzd8-mediated mito–ER contacts improves organismal fitness and mitigates Aβ42 toxicity

    Victoria L Hewitt, Leonor Miller-Fleming, Madeleine J Twyning, Simonetta Andreazza, Francesca Mattedi, Julien Prudent, Franck Polleux, Alessio Vagnoni, Alexander J Whitworth

    Victoria L Hewitt ... Alexander J Whitworth

    Published 13 July 2022

    The authors provide the first description of the impact of reducing pdzd8-mediated mito–ER contacts which prolongs lifespan, reduces age-related locomotor decline, and protects against mitochondrial toxins. pdzd8 loss is also protective against neuronal toxicity from Aβ42.

  • ERK2 MAP kinase regulates SUFU binding by multisite phosphorylation of GLI1
    Open Access
    ERK2 MAP kinase regulates SUFU binding by multisite phosphorylation of GLI1

    A Jane Bardwell, Beibei Wu, Kavita Y Sarin, Marian L Waterman, Scott X Atwood, Lee Bardwell

    A Jane Bardwell ... Lee Bardwell

    Published 13 July 2022

    As a mechanism of crosstalk, potentially relevant to cancer and developmental signaling, ERK2 MAP kinase phosphorylates the Hedgehog-pathway transcription factor GLI1 on three sites, promoting release of the negative regulator SUFU and the consequent activation of GLI1.

  • ScRNA-seq expression of <em>IFI27</em> and <em>APOC2</em> identifies four alveolar macrophage superclusters in healthy BALF
    Open Access
    ScRNA-seq expression of IFI27 and APOC2 identifies four alveolar macrophage superclusters in healthy BALF

    Xin Li, Fred W Kolling, Daniel Aridgides, Diane Mellinger, Alix Ashare, Claudia V Jakubzick

    Xin Li ... Claudia V Jakubzick

    Published 12 July 2022

    There are at least 14 AM subtypes; their frequency, along with other immune cells, is highly conserved across individuals, suggesting a specific niche exists for each leukocyte population.

  • Heparan sulfate proteoglycans mediate prion-like α-synuclein toxicity in Parkinson’s in vivo models
    Open Access
    Heparan sulfate proteoglycans mediate prion-like α-synuclein toxicity in Parkinson’s in vivo models

    Merry Chen, Julie Vincent, Alexis Ezeanii, Saurabh Wakade, Shobha Yerigenahally, Danielle E Mor

    Merry Chen ... Danielle E Mor

    Published 5 July 2022

    This study offers new Caenorhabditis elegans models in which feeding with α-synuclein pre-formed fibrils results in prion-like aggregation of host α-synuclein and dopamine neuron degeneration, and these disease phenotypes are regulated by the heparan sulfate proteoglycan pathway.

  • Multi-omics profiling identifies a deregulated FUS-MAP1B axis in ALS/FTD–associated UBQLN2 mutants
    Open Access
    Multi-omics profiling identifies a deregulated FUS-MAP1B axis in ALS/FTD–associated UBQLN2 mutants

    Laura Strohm, Zehan Hu, Yongwon Suk, Alina Rühmkorf, Erin Sternburg, Vanessa Gattringer, Henrick Riemenschneider, Riccardo Berutti, Elisabeth Graf, Jochen H Weishaupt, Monika S Brill, Angelika B Harbauer, Dorothee Dormann, Jörn Dengjel, Dieter Edbauer, Christian Behrends

    Laura Strohm ... Christian Behrends

    Published 1 July 2022

    Analysis of ALS patient-derived and engineered cells revealed that mutant UBQLN2 increases mRNA and protein of MAP1B which is mediated by dephosphorylation of FUS within its RNA-binding domain.

  • STAT3 in tumor fibroblasts promotes an immunosuppressive microenvironment in pancreatic cancer
    Open Access
    STAT3 in tumor fibroblasts promotes an immunosuppressive microenvironment in pancreatic cancer

    Julia E Lefler, Catherine B MarElia-Bennett, Katie A Thies, Blake E Hildreth, Sudarshana M Sharma, Jason R Pitarresi, Lu Han, Caroline Everett, Christopher Koivisto, Maria C Cuitino, Cynthia D Timmers, Elizabeth O’Quinn, Melodie Parrish, Martin J Romeo, Amanda J Linke, G Aaron Hobbs, Gustavo Leone, Denis C Guttridge, Teresa A Zimmers, Gregory B Lesinski, Michael C Ostrowski

    Julia E Lefler ... Michael C Ostrowski

    Published 8 July 2022

    Using a dual recombinase mouse model of pancreatic cancer, investigators uncover genetic evidence for the role of STAT3 signaling in cancer-associated fibroblasts in promoting tumor progression and an immunosuppressive microenvironment.

  • CryoEM of endogenous mammalian V-ATPase interacting with the TLDc protein mEAK-7
    Open Access
    CryoEM of endogenous mammalian V-ATPase interacting with the TLDc protein mEAK-7

    Yong Zi Tan, Yazan M Abbas, Jing Ze Wu, Di Wu, Kristine A Keon, Geoffrey G Hesketh, Stephanie A Bueler, Anne-Claude Gingras, Carol V Robinson, Sergio Grinstein, John L Rubinstein

    Yong Zi Tan ... John L Rubinstein

    Published 6 July 2022

    The structure of mammalian V-ATPase with mEAK-7 shows how a TLDc domain-containing protein can bind the proton pump to form an activity-sensitive interaction.

  • Analyzing efficacy, stability, and safety of AAV-mediated optogenetic hearing restoration in mice
    Open Access
    Analyzing efficacy, stability, and safety of AAV-mediated optogenetic hearing restoration in mice

    Burak Bali, Eva Gruber-Dujardin, Kathrin Kusch, Vladan Rankovic, Tobias Moser

    Burak Bali ... Tobias Moser

    Published 5 May 2022

    This longitudinal study revealed stable expression of the fast-gating channelrhodopsin f-Chrimson in cochlear neurons of mice over at least 2 yr upon a single postnatal AAV dosing of the cochlea.

  • Proteins implicated in muscular dystrophy and cancer are functional constituents of the centrosome
    Open Access
    Proteins implicated in muscular dystrophy and cancer are functional constituents of the centrosome

    Lilli Winter, Monika Kustermann, Büsra Ernhofer, Harald Höger, Reginald E Bittner, Wolfgang M Schmidt

    Lilli Winter ... Wolfgang M Schmidt

    Published 5 July 2022

    This study demonstrates that the muscular dystrophy-associated proteins dystrophin, utrophin, dysferlin, and calpain-3 localize to the centrosome and that their absence leads to excess centrosomes, compromised nuclear morphology, impaired centrosome orientation, and defective microtubule nucleation.

  • <em>Drosophila</em> insulator proteins exhibit in vivo liquid–liquid phase separation properties
    Open Access
    Drosophila insulator proteins exhibit in vivo liquid–liquid phase separation properties

    Bright Amankwaa, Todd Schoborg, Mariano Labrador

    Bright Amankwaa ... Mariano Labrador

    Published 19 July 2022

    Drosophila insulator proteins and the cohesin subunit Rad21 coalesce in vivo to form liquid-droplet condensates, suggesting that liquid–liquid phase separation mediates their function in 3D genome organization.

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