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Excessive tubulin polyglutamylation causes neurodegeneration and perturbs neuronal transport

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Excessive tubulin polyglutamylation causes neurodegeneration and perturbs neuronal transport. / Magiera, Maria M; Bodakuntla, Satish; Žiak, Jakub; Lacomme, Sabrina; Marques Sousa, Patricia; Leboucher, Sophie; Hausrat, Torben J; Bosc, Christophe; Andrieux, Annie; Kneussel, Matthias; Landry, Marc; Calas, André; Balastik, Martin; Janke, Carsten.

In: EMBO J, Vol. 37, No. 23, 03.12.2018, p. e100440.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Magiera, MM, Bodakuntla, S, Žiak, J, Lacomme, S, Marques Sousa, P, Leboucher, S, Hausrat, TJ, Bosc, C, Andrieux, A, Kneussel, M, Landry, M, Calas, A, Balastik, M & Janke, C 2018, 'Excessive tubulin polyglutamylation causes neurodegeneration and perturbs neuronal transport', EMBO J, vol. 37, no. 23, pp. e100440. https://doi.org/10.15252/embj.2018100440

APA

Magiera, M. M., Bodakuntla, S., Žiak, J., Lacomme, S., Marques Sousa, P., Leboucher, S., Hausrat, T. J., Bosc, C., Andrieux, A., Kneussel, M., Landry, M., Calas, A., Balastik, M., & Janke, C. (2018). Excessive tubulin polyglutamylation causes neurodegeneration and perturbs neuronal transport. EMBO J, 37(23), e100440. https://doi.org/10.15252/embj.2018100440

Vancouver

Magiera MM, Bodakuntla S, Žiak J, Lacomme S, Marques Sousa P, Leboucher S et al. Excessive tubulin polyglutamylation causes neurodegeneration and perturbs neuronal transport. EMBO J. 2018 Dec 3;37(23):e100440. https://doi.org/10.15252/embj.2018100440

Bibtex

@article{edd28734693b44dfac7ec900fc6c5553,
title = "Excessive tubulin polyglutamylation causes neurodegeneration and perturbs neuronal transport",
abstract = "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.",
keywords = "Journal Article",
author = "Magiera, {Maria M} and Satish Bodakuntla and Jakub {\v Z}iak and Sabrina Lacomme and {Marques Sousa}, Patricia and Sophie Leboucher and Hausrat, {Torben J} and Christophe Bosc and Annie Andrieux and Matthias Kneussel and Marc Landry and Andr{\'e} Calas and Martin Balastik and Carsten Janke",
note = "{\textcopyright} 2018 The Authors.",
year = "2018",
month = dec,
day = "3",
doi = "10.15252/embj.2018100440",
language = "English",
volume = "37",
pages = "e100440",
journal = "EMBO J",
issn = "0261-4189",
publisher = "NATURE PUBLISHING GROUP",
number = "23",

}

RIS

TY - JOUR

T1 - Excessive tubulin polyglutamylation causes neurodegeneration and perturbs neuronal transport

AU - Magiera, Maria M

AU - Bodakuntla, Satish

AU - Žiak, Jakub

AU - Lacomme, Sabrina

AU - Marques Sousa, Patricia

AU - Leboucher, Sophie

AU - Hausrat, Torben J

AU - Bosc, Christophe

AU - Andrieux, Annie

AU - Kneussel, Matthias

AU - Landry, Marc

AU - Calas, André

AU - Balastik, Martin

AU - Janke, Carsten

N1 - © 2018 The Authors.

PY - 2018/12/3

Y1 - 2018/12/3

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.15252/embj.2018100440

DO - 10.15252/embj.2018100440

M3 - SCORING: Journal article

C2 - 30420556

VL - 37

SP - e100440

JO - EMBO J

JF - EMBO J

SN - 0261-4189

IS - 23

ER -