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Accepted Manuscript
Research Article
Tubulin polyglutamylation is a general traffic control mechanism in hippocampal neurons
Satish Bodakuntla, Anne Schnitzler, Cristopher Villablanca, Christian Gonzalez-Billault, Ivan Bieche, Carsten Janke, Maria M. Magiera
Journal of Cell Science 2020 : jcs.241802 doi: 10.1242/jcs.241802 Published 13 January 2020
Satish Bodakuntla
Institut Curie, PSL Research University, CNRS UMR3348, F-91405 Orsay, FranceUniversité Paris Sud, Université Paris-Saclay, CNRS UMR3348, F-91405 Orsay, France
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  • ORCID record for Satish Bodakuntla
Anne Schnitzler
Institut Curie, PSL Research University, Department of Genetics, F-75005, Paris, France
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  • ORCID record for Anne Schnitzler
Cristopher Villablanca
Center for Geroscience, Brain Health and Metabolism (GERO), Santiago, ChileDepartment of Biology, Faculty of Sciences, University of Chile, Santiago, Chile
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Christian Gonzalez-Billault
Center for Geroscience, Brain Health and Metabolism (GERO), Santiago, ChileDepartment of Biology, Faculty of Sciences, University of Chile, Santiago, Chile
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  • ORCID record for Christian Gonzalez-Billault
Ivan Bieche
Institut Curie, PSL Research University, Department of Genetics, F-75005, Paris, FranceUniversité Paris Descartes, Sorbonne Paris Cité, F-75005, Paris, France
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Carsten Janke
Institut Curie, PSL Research University, CNRS UMR3348, F-91405 Orsay, FranceUniversité Paris Sud, Université Paris-Saclay, CNRS UMR3348, F-91405 Orsay, France
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  • For correspondence: Maria.Magiera@curie.fr Carsten.Janke@curie.fr
Maria M. Magiera
Institut Curie, PSL Research University, CNRS UMR3348, F-91405 Orsay, FranceUniversité Paris Sud, Université Paris-Saclay, CNRS UMR3348, F-91405 Orsay, France
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  • For correspondence: Maria.Magiera@curie.fr Carsten.Janke@curie.fr
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Abstract

Neurons are highly complex cells that heavily rely on intracellular transport to distribute a range of functionally essential cargoes within the cell. Posttranslational modifications of tubulin are emerging mechanisms to regulate microtubule functions, but their impact on neuronal transport is only marginally understood. Here we have systematically studied the impact of posttranslational polyglutamylation on axonal transport. In cultured hippocampal neurons, deletion of a single deglutamylase, CCP1, is sufficient to induce abnormal accumulation of polyglutamylation, i.e. hyperglutamylation. We next investigated how hyperglutamylation affects axonal transport of a range of functionally different neuronal cargoes: mitochondria, lysosomes, LAMP1 endosomes and BDNF vesicles. Strikingly, we found a reduced motility for all these cargoes, suggesting that polyglutamylation could act as a central regulator of cargo transport in neurons. This, together with the recent discovery that hyperglutamylation induces neurodegeneration, makes it likely that perturbed neuronal traffic could be one of the central molecular causes underlying this novel type of degeneration.

  • Received November 15, 2019.
  • Accepted December 23, 2019.
  • © 2020. Published by The Company of Biologists Ltd
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Keywords

  • Axonal transport
  • Microtubules
  • Neuronal transport
  • Polyglutamylation
  • Tubulin code
  • Tubulin posttranslational modifications

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Accepted Manuscript
Research Article
Tubulin polyglutamylation is a general traffic control mechanism in hippocampal neurons
Satish Bodakuntla, Anne Schnitzler, Cristopher Villablanca, Christian Gonzalez-Billault, Ivan Bieche, Carsten Janke, Maria M. Magiera
Journal of Cell Science 2020 : jcs.241802 doi: 10.1242/jcs.241802 Published 13 January 2020
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Accepted Manuscript
Research Article
Tubulin polyglutamylation is a general traffic control mechanism in hippocampal neurons
Satish Bodakuntla, Anne Schnitzler, Cristopher Villablanca, Christian Gonzalez-Billault, Ivan Bieche, Carsten Janke, Maria M. Magiera
Journal of Cell Science 2020 : jcs.241802 doi: 10.1242/jcs.241802 Published 13 January 2020

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