Počet záznamů: 1  

Excessive tubulin polyglutamylation causes neurodegeneration and perturbs neuronal transport

  1. 1.
    0498744 - FGÚ 2019 RIV GB eng J - Článek v odborném periodiku
    Magiera, M. M. - Bodakuntla, S. - Žiak, Jakub - Lacomme, S. - Sousa, P. M. - Leboucher, S. - Hausrat, T. J. - Bosc, Ch. - Andrieux, A. - Kneussel, M. - Landry, M. - Calas, A. - Balaštík, Martin - Janke, C.
    Excessive tubulin polyglutamylation causes neurodegeneration and perturbs neuronal transport.
    EMBO Journal. Roč. 37, č. 23 (2018), č. článku e100440. ISSN 0261-4189. E-ISSN 1460-2075
    Grant CEP: GA ČR(CZ) GA16-15915S
    Institucionální podpora: RVO:67985823
    Klíčová slova: axonal transport * neurodegeneration * tubulin code * tubulin polyglutamylation * tubulin posttranslational modifications
    Obor OECD: Neurosciences (including psychophysiology
    Impakt faktor: 11.227, rok: 2018

    Posttranslational modifications of tubulin are emerging regulators of microtubule functions. We have shown earlier that upregulated polyglutamylation is linked to rapid degeneration of Purkinje cells in mice with a mutation in the deglutamylating enzyme CCP1. How polyglutamylation leads to degeneration, whether it affects multiple neuron types, or which physiological processes it regulates in healthy neurons has remained unknown. Here, we demonstrate that excessive polyglutamylation induces neurodegeneration in a cell‐autonomous manner and can occur in many parts of the central nervous system. Degeneration of selected neurons in CCP1‐deficient mice can be fully rescued by simultaneous knockout of the counteracting polyglutamylase TTLL1. Excessive polyglutamylation reduces the efficiency of neuronal transport in cultured hippocampal neurons, suggesting that impaired cargo transport plays an important role in the observed degenerative phenotypes. We thus establish polyglutamylation as a cell‐autonomous mechanism for neurodegeneration that might be therapeutically accessible through manipulation of the enzymes that control this posttranslational modification.
    Trvalý link: http://hdl.handle.net/11104/0291011

     
     
Počet záznamů: 1  

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