Trafficking through Rab11 Endosomes Is Required for Cellularization during Drosophila Embryogenesis

AbstractBackground: Embryonic cleavage leads to the formation of an epithelial layer during development. In Drosophila, the process is specialized and called cellularization. The trafficking pathways that underlie this process and that are responsible for the mobilization of membrane pools, however, remain poorly understood.Results: We provide functional evidence for the role of endocytic trafficking through Rab11 endosomes in remobilizing vesicular membrane pools to ensure lateral membrane growth. Part of the membrane stems from endocytosed apical material. Mutants in the endocytic regulators rab5 and shibire/dynamin inhibit basal-lateral membrane growth, and apical endocytosis is blocked in shibire mutants. In addition, shibire controls vesicular trafficking through Rab11-positive endosomes. In shibire mutants, the transmembrane protein Neurotactin follows the secretory pathway normally but is not properly inserted in the plasma membrane and accumulates instead in Rab11 subapical endosomes. Consistent with a direct role of shibire in vesicular trafficking through Rab11 endosomes, Shibire is enriched in this compartment. Moreover, we show by electron microscopy the large accumulation of intracellular coated pits on subapical endocytic structures in shibire mutants. Finally, we show that Rab11 is essential for membrane growth and invagination during cellularization.Conclusion: Together, the data show that endocytic trafficking is required for basal-lateral membrane growth during cellularization. We identify Rab11 endosomes as key trafficking intermediates that control vesicle exocytosis and membrane growth during cellularization. This pathway may be required in other morphogenetic processes characterized by the growth of a membrane domain

Sensory-motor deficits and neurofilament disorganization in gigaxonin-null mice

International audienceABSTRACT: BACKGROUND: Giant Axonal Neuropathy (GAN) is a fatal neurodegenerative disorder with early onset characterized by a severe deterioration of the peripheral and central nervous system, involving both the motor and sensory tracts and leading to ataxia, speech defect and intellectual disabilities. The broad deterioration of the nervous system is accompanied by a generalized disorganization of the intermediate filaments, including neurofilaments in neurons, but the implication of this defect in disease onset or progression remains unknown. The identification of gigaxonin, the substrate adaptor of an E3 ubiquitin ligase, as the defective protein in GAN allows us to now investigate the crucial role of the gigaxonin-E3 ligase in sustaining neuronal and intermediate filament integrity. To study the mechanisms controlled by gigaxonin in these processes and to provide a relevant model to test the therapeutic approaches under development for GAN, we generated a Gigaxonin-null mouse by gene targeting. RESULTS: We investigated for the first time in Gigaxonin-null mice the deterioration of the motor and sensory functions over time as well as the spatial disorganization of neurofilaments. We showed that gigaxonin depletion in mice induces mild but persistent motor deficits starting at 60 weeks of age in the 129/SvJ-genetic background, while sensory deficits were demonstrated in C57BL/6 animals. In our hands, another gigaxonin-null mouse did not display the early and severe motor deficits reported previously. No apparent neurodegeneration was observed in our knock-out mice, but dysregulation of neurofilaments in proximal and distal axons was massive. Indeed, neurofilaments were not only more abundant but they also showed the abnormal increase in diameter and misorientation that are characteristics of the human pathology. CONCLUSIONS: Together, our results show that gigaxonin depletion in mice induces mild motor and sensory deficits but recapitulates the severe neurofilament dysregulation seen in patients. Our model will allow investigation of the role of the gigaxonin-E3 ligase in organizing neurofilaments and may prove useful in understanding the pathological processes engaged in other neurodegenerative disorders characterized by accumulation of neurofilaments and dysfunction of the Ubiquitin Proteasome System, such as Amyotrophic Lateral Sclerosis, Huntington's, Alzheimer's and Parkinson's diseases

Débat sur les perspectives économiques à court terme du 10 octobre 2002

Les prévisions occupent une place particulière dans le débat public en économie. Elles sont généralement considérées comme des prédictions, qualifiées fréquemment d’optimistes ou de pessimistes, comme si elles dépendaient de l’humeur des équipes qui les réalisent. Certes, en un sens, la prévision est un art tant elle dépend des signes précurseurs que nous livre le présent, de l’interprétation des évolutions en cours, de la capacité des économistes de sélectionner les informations pertinentes parmi celles, multiples, dont l’intérêt n’est qu’anecdotique. Mais elle est surtout une science puisqu’elle consiste à déduire des informations dont on dispose sur le présent une vision de l’avenir. Elle ne peut être formulée en dehors d’un cadre général d’interprétation, c’est-à-dire d’une théorie qui met en relation les informations que l’on privilégie et les variables que l’on cherche à prévoir. [Premier paragraphe

Débat sur les perspectives économiques à court terme du 10 Octobre 2002.

Cette publication n'a pas de résumé