153 results found
    1. Genetics and Genomics

    miR-1 coordinately regulates lysosomal v-ATPase and biogenesis to impact proteotoxicity and muscle function during aging

    Isabelle Schiffer et al.
    Coordinate control of lysosomal v-ATPase subunits and biogenesis factor TFEB by miR-1 identifies a key regulatory axis with strong links to age-related proteotoxic disease.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    Control of the structural landscape and neuronal proteotoxicity of mutant Huntingtin by domains flanking the polyQ tract

    Koning Shen et al.
    The polyQ tract of pathogenic Huntingtin causes aggregation when expanded in Huntington’s disease, but its two flanking domains control its conformational landscape, proteostasis and neurotoxicity.
    1. Cell Biology

    Nuclear export of misfolded SOD1 mediated by a normally buried NES-like sequence reduces proteotoxicity in the nucleus

    Yongwang Zhong et al.
    Cellular and genetic approaches reveal that exposure of a normally buried nuclear export signal (NES)-like sequence mediates export of ALS-linked mutant and misfolded wild-type SOD1 to the cytoplasm by CRM1.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    Proteotoxicity from aberrant ribosome biogenesis compromises cell fitness

    Blake W Tye et al.
    Rapidly proliferating cells are at risk of compromised cell fitness due to proteostasis collapse from perturbations that interfere with ribosome biogenesis.
    1. Biochemistry and Chemical Biology
    2. Genetics and Genomics

    Therapeutic genetic variation revealed in diverse Hsp104 homologs

    Zachary M March et al.
    Exploring natural Hsp104 variation reveals unexpected tuning of a passive activity that inhibits aggregation of specific substrates to selectively counter TDP-43 or alpha-synuclein proteotoxicity connected to neurodegenerative disease.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    Cell-based HTS identifies a chemical chaperone for preventing ER protein aggregation and proteotoxicity

    Keisuke Kitakaze et al.
    Cell-based high-throughput screening identifies IBT21 as a chemical chaperone, that inhibits ER protein aggregation and prevents the cell death caused by a proteotoxin, the aggregation-prone prion protein.
    1. Cell Biology

    Inadequate BiP availability defines endoplasmic reticulum stress

    Milena Vitale et al.
    The extent of (proteotoxic) endoplasmic reticulum stress, and the ensuing unfolded protein response activation, are commensurate with the extent of the chaperone BiP being sequestered by its client proteins.
    1. Immunology and Inflammation
    2. Physics of Living Systems

    Label-free imaging of immune cell dynamics in the living retina using adaptive optics

    Aby Joseph et al.
    Immune cell motility and vascular response are imaged in vivo and label free in the CNS for the first time, using high-resolution phase-contrast adaptive optics retinal imaging.
    1. Neuroscience

    Optical electrophysiology for probing function and pharmacology of voltage-gated ion channels

    Hongkang Zhang et al.
    Optogenetic tools enable sophisticated measurements of a voltage-gated sodium channel implicated in pain, as well as high-throughput screening of candidate channel blockers.
    1. Cell Biology
    2. Chromosomes and Gene Expression

    A ribosome assembly stress response regulates transcription to maintain proteome homeostasis

    Benjamin Albert et al.
    Ribosome assembly is monitored to promote proteostatis through a system whereby unassembled ribosomal proteins lead to activation of heat shock factor 1 and inactivation of the RP gene activator Ifh1.

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