Journal article
The EMBO journal, 2018
APA
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Shashi, V., Magiera, M., Klein, D., Zaki, M., Schoch, K., Rudnik-Schöneborn, S., … Senderek, J. (2018). Loss of tubulin deglutamylase CCP1 causes infantile‐onset neurodegeneration. The EMBO Journal.
Chicago/Turabian
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Shashi, V., M. Magiera, D. Klein, M. Zaki, K. Schoch, S. Rudnik-Schöneborn, A. Norman, et al. “Loss of Tubulin Deglutamylase CCP1 Causes Infantile‐Onset Neurodegeneration.” The EMBO journal (2018).
MLA
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Shashi, V., et al. “Loss of Tubulin Deglutamylase CCP1 Causes Infantile‐Onset Neurodegeneration.” The EMBO Journal, 2018.
BibTeX Click to copy
@article{v2018a,
title = {Loss of tubulin deglutamylase CCP1 causes infantile‐onset neurodegeneration},
year = {2018},
journal = {The EMBO journal},
author = {Shashi, V. and Magiera, M. and Klein, D. and Zaki, M. and Schoch, K. and Rudnik-Schöneborn, S. and Norman, A. and Neto, O. Lopes Abath and Dusl, M. and Yuan, Xidi and Bartesaghi, Luca and Marco, P. De and Alfares, A. and Marom, R. and Arold, S. and Guzmán-Vega, Francisco J. and Pena, L. and Smith, E. and Steinlin, M. and Babiker, Mohamed O E and Mohassel, P. and Foley, A. and Donkervoort, S. and Kaur, R. and Ghosh, P. and Stanley, Valentina and Musaev, D. and Nava, C. and Mignot, C. and Keren, B. and Scala, M. and Tassano, E. and Picco, P. and Doneda, P. and Fiorillo, C. and Issa, M. and Alassiri, A. and Alahmad, A. and Gerard, A. and Liu, P. and Yang, Yaping and Ertl-Wagner, B. and Kranz, P. and Wentzensen, I. and Stucka, R. and Stong, N. and Allen, A. and Goldstein, D. and Schoser, B. and Rösler, K. and Alfadhel, M. and Capra, V. and Chrast, R. and Strom, T. and Kamsteeg, E. and Bönnemann, C. and Gleeson, J. and Martini, R. and Janke, C. and Senderek, J.}
}
A set of glutamylases and deglutamylases controls levels of tubulin polyglutamylation, a prominent post‐translational modification of neuronal microtubules. Defective tubulin polyglutamylation was first linked to neurodegeneration in the Purkinje cell degeneration (pcd) mouse, which lacks deglutamylase CCP1, displays massive cerebellar atrophy, and accumulates abnormally glutamylated tubulin in degenerating neurons. We found biallelic rare and damaging variants in the gene encoding CCP1 in 13 individuals with infantile‐onset neurodegeneration and confirmed the absence of functional CCP1 along with dysregulated tubulin polyglutamylation. The human disease mainly affected the cerebellum, spinal motor neurons, and peripheral nerves. We also demonstrate previously unrecognized peripheral nerve and spinal motor neuron degeneration in pcd mice, which thus recapitulated key features of the human disease. Our findings link human neurodegeneration to tubulin polyglutamylation, entailing this post‐translational modification as a potential target for drug development for neurodegenerative disorders.