Tubulin tyrosination is required for the proper organization and pathfinding of the growth cone
| Autor: | Julie L. M. Moreau, Stéphanie Backer, Didier Job, Annie Andrieux, Séverine Marcos, Evelyne Bloch-Gallego |
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| Přispěvatelé: | Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Collaboration, Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier - Grenoble 1 (UJF) - CHU Grenoble - Institut National de la Santé et de la Recherche Médicale (INSERM), Andrieux, Annie |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
MESH : Tyrosine
rac1 GTP-Binding Protein MESH : Actins lcsh:Medicine MESH: Tubulin GTP Phosphohydrolases MESH: Tyrosine MESH : Cytoskeleton Mice 0302 clinical medicine Tubulin Myosin MESH: Animals Cytoskeleton lcsh:Science MESH: Nonmuscle Myosin Type IIB 0303 health sciences Multidisciplinary Nonmuscle Myosin Type IIB biology MESH : Tubulin Neuroscience/Neurodevelopment Cell biology [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] Collapsin response mediator protein family Filopodia Research Article MESH: Axons MESH: GTP Phosphohydrolases Neurite Cell Biology/Neuronal Signaling Mechanisms Growth Cones Cell Biology/Developmental Molecular Mechanisms MESH : Axons macromolecular substances MESH : Growth Cones MESH: Actins 03 medical and health sciences MESH : rac1 GTP-Binding Protein Microtubule Cell Biology/Cytoskeleton MESH : Mice Neuroscience/Neuronal Signaling Mechanisms MESH: Cytoskeleton Animals [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] Growth cone MESH: Mice 030304 developmental biology MESH : Protein Processing Post-Translational MESH : Nonmuscle Myosin Type IIB MESH: rac1 GTP-Binding Protein lcsh:R MESH: Growth Cones Actins Axons Developmental Biology/Neurodevelopment MESH: Protein Processing Post-Translational biology.protein Developmental Biology/Cell Differentiation Tyrosine lcsh:Q MESH : Animals MESH : GTP Phosphohydrolases Protein Processing Post-Translational 030217 neurology & neurosurgery |
| Zdroj: | PLoS ONE PLoS ONE, Public Library of Science, 2009, 4 (4), pp.e5405. ⟨10.1371/journal.pone.0005405⟩ PLoS ONE, Vol 4, Iss 4, p e5405 (2009) PLoS ONE, Public Library of Science, 2009, 4 (4), pp.e5405. 〈10.1371/journal.pone.0005405〉 PLoS ONE, 2009, 4 (4), pp.e5405. ⟨10.1371/journal.pone.0005405⟩ |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0005405⟩ |
| Popis: | International audience; BACKGROUND: During development, neuronal growth cones integrate diffusible and contact guidance cues that are conveyed to both actin and microtubule (MT) cytoskeletons and ensure axon outgrowth and pathfinding. Although several post-translational modifications of tubulin have been identified and despite their strong conservation among species, their physiological roles during development, especially in the nervous sytem, are still poorly understood. METHODOLOGY/FINDINGS: Here, we have dissected the role of a post-translational modification of the last amino acid of the alpha-tubulin on axonal growth by analyzing the phenotype of precerebellar neurons in Tubulin tyrosin ligase knock-out mice (TTL(-/-)) through in vivo, ex vivo and in vitro analyses. TTL(-/-) neurons are devoid of tyrosinated tubulin. Their pathway shows defects in vivo, ex vivo, in hindbrains open-book preparations or in vitro, in a collagen matrix. Their axons still orient toward tropic cues, but they emit supernumerary branches and their growth cones are enlarged and exhibit an emission of mis-oriented filopodia. Further analysis of the TTL(-/-) growth cone intracellular organization also reveals that the respective localization of actin and MT filaments is disturbed, with a decrease in the distal accumulation of Myosin IIB, as well as a concomitant Rac1 over-activation in the hindbrain. Pharmacological inhibition of Rac1 over-activation in TTL(-/-) neurons can rescue Myosin IIB localization. CONCLUSIONS/SIGNIFICANCE: In the growth cone, we propose that tubulin tyrosination takes part in the relative arrangement of actin and MT cytoskeletons, in the regulation of small GTPases activity, and consequently, in the proper morphogenesis, organization and pathfinding of the growth cone during development. |
| Databáze: | OpenAIRE |
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