PMID: identifiant
de la référence Pubmed : |
 |
 (19404406)  |
|
| titre : |
|
Tubulin tyrosination is required for the proper organization and pathfinding of the growth cone. |
|
| auteur(s) : |
|
Séverine Marcos1, Julie Moreau1, Stéphanie Backer1, Didier Job2, Annie Andrieux2, Evelyne Bloch-Gallego ( ) 1, Collaboration Collaboration(s) |
|
| laboratoire : |
|
|
|
| résumé : |
|
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. |
|
| domaine : |
|
Sciences du Vivant/Neurosciences
|
|
langue du texte
intégral : |
|
Anglais |
|
| ISSN : |
|
1932-6203 |
|
|
| Équipe(s) de recherche : |
|
INSERM U836, équipe 1, Physiopathologie du cytosquelette |
|
|
| type de publication : |
|
Articles dans des revues avec comité de lecture |
|
| DOI : |
|
10.1371/journal.pone.0005405 |
|
| journal : |
|
|
|
| Audience : |
|
internationale |
|
| date de publication : |
|
2009 |
|
| volume : |
|
4 |
|
| numéro : |
|
4 |
|
| page, identifiant, ... : |
|
e5405 |
|
|
| Descripteur(s) MeSH : |
|
Actins – Animals – Axons – Cytoskeleton – GTP Phosphohydrolases – Growth Cones – Mice – Nonmuscle Myosin Type IIB – Protein Processing – Post-Translational – Tubulin – Tyrosine – rac1 GTP-Binding Protein |
|
