61 results found
    1. Neuroscience

    Rem2 stabilizes intrinsic excitability and spontaneous firing in visual circuits

    Anna R Moore et al.
    In vivo and ex vivo analysis of the activity-regulated gene Rem2 in the mouse visual system sheds new light on the contribution of intrinsic excitability in circuit plasticity.
    1. Structural Biology and Molecular Biophysics

    Ligand recognition and gating mechanism through three ligand-binding sites of human TRPM2 channel

    Yihe Huang et al.
    High-resolution structures of human TRPM2 in different functional states provided the mechanism underlying ligand recognition, channel activation and inhibition.
    1. Neuroscience

    Microglia TREM2R47H Alzheimer-linked variant enhances excitatory transmission and reduces LTP via increased TNF-α levels

    Siqiang Ren et al.
    Analysis of rats carrying the microglia gene and Alzheimer risk factor Trem2R47H variant shows increased glutamatergic transmission via supraphysiological TNF-α brain concentrations, linking a microglia pathogenic variant to neuronal dysfunction.
    1. Structural Biology and Molecular Biophysics
    2. Neuroscience

    Neurodegenerative disease mutations in TREM2 reveal a functional surface and distinct loss-of-function mechanisms

    Daniel L Kober et al.
    Structural, biophysical, and functional analyses reveal that mutations in TREM2 trigger either misfolding or reduced binding to cell-surface glycosaminoglycans, which segregate with neurodegenerative disease link and highlight a functional surface linked to the pathogenesis of Alzheimer's disease.
    1. Structural Biology and Molecular Biophysics

    Structure of a TRPM2 channel in complex with Ca2+ explains unique gating regulation

    Zhe Zhang et al.
    The 3Å structure and correlated functional analysis of the TRPM2 cation channel from Nematostella vectensis shed light on the molecular mechanisms of TRPM2 regulation by intra- and extracellular Ca2+, and of inactivation of human TRPM2.
    1. Structural Biology and Molecular Biophysics

    Enzyme activity and selectivity filter stability of ancient TRPM2 channels were simultaneously lost in early vertebrates

    Iordan Iordanov et al.
    Invertebrate TRPM2 channels have stable pores but act as chanzymes that hydrolyze their activating ligand ADP ribose (ADPR), whereas vertebrate TRPM2 channels are catalytically dead but undergo pore inactivation.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    The proposed channel-enzyme transient receptor potential melastatin 2 does not possess ADP ribose hydrolase activity

    Iordan Iordanov et al.
    TRPM2 is simply a ligand gated channel and does not to possess enzymatic activity, even though it shows sequence similarity to Nudix hydrolases.
    1. Immunology and Inflammation
    2. Neuroscience

    Differential accumulation of storage bodies with aging defines discrete subsets of microglia in the healthy brain

    Jeremy Carlos Burns et al.
    Two novel subsets of microglia identified by their unique autofluorescence profiles differ in their subcellular organization, proteomic signatures and in their response to aging and lysosomal dysfunction.
    1. Neuroscience

    A MAC2-positive progenitor-like microglial population is resistant to CSF1R inhibition in adult mouse brain

    Lihong Zhan et al.
    A hidden population of microglial progenitors with distinct transcriptomic signatures are among homeostatic microglia in adult mouse brain.
    1. Structural Biology and Molecular Biophysics

    Global alignment and assessment of TRP channel transmembrane domain structures to explore functional mechanisms

    Katherine E Huffer et al.
    Structure-based alignment of TRP channels enables comparison of structural changes, ion permeation pathways and ligand-binding sites and reveals over-representation of structures that represent non-conducting states.

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