Vezatin is essential for dendritic spine morphogenesis and functional synaptic maturation.

International audienceVezatin is an integral membrane protein associated with cell-cell adhesion complex and actin cytoskeleton. It is expressed in the developing and mature mammalian brain, but its neuronal function is unknown. Here, we show that Vezatin localizes in spines in mature mouse hippocampal neurons and codistributes with PSD95, a major scaffolding protein of the excitatory postsynaptic density. Forebrain-specific conditional ablation of Vezatin induced anxiety-like behavior and impaired cued fear-conditioning memory response. Vezatin knock-down in cultured hippocampal neurons and Vezatin conditional knock-out in mice led to a significantly increased proportion of stubby spines and a reduced proportion of mature dendritic spines. PSD95 remained tethered to presynaptic terminals in Vezatin-deficient hippocampal neurons, suggesting that the reduced expression of Vezatin does not compromise the maintenance of synaptic connections. Accordingly, neither the amplitude nor the frequency of miniature EPSCs was affected in Vezatin-deficient hippocampal neurons. However, the AMPA/NMDA ratio of evoked EPSCs was reduced, suggesting impaired functional maturation of excitatory synapses. These results suggest a role of Vezatin in dendritic spine morphogenesis and functional synaptic maturation

RAB-5 Controls the Cortical Organization and Dynamics of PAR Proteins to Maintain C. elegans Early Embryonic Polarity

In all organisms, cell polarity is fundamental for most aspects of cell physiology. In many species and cell types, it is controlled by the evolutionarily conserved PAR-3, PAR-6 and aPKC proteins, which are asymmetrically localized at the cell cortex where they define specific domains. While PAR proteins define the antero-posterior axis of the early C. elegans embryo, the mechanism controlling their asymmetric localization is not fully understood. Here we studied the role of endocytic regulators in embryonic polarization and asymmetric division. We found that depleting the early endosome regulator RAB-5 results in polarity-related phenotypes in the early embryo. Using Total Internal Reflection Fluorescence (TIRF) microscopy, we observed that PAR-6 is localized at the cell cortex in highly dynamic puncta and depleting RAB-5 decreased PAR-6 cortical dynamics during the polarity maintenance phase. Depletion of RAB-5 also increased PAR-6 association with clathrin heavy chain (CHC-1) and this increase depended on the presence of the GTPase dynamin, an upstream regulator of endocytosis. Interestingly, further analysis indicated that loss of RAB-5 leads to a disorganization of the actin cytoskeleton and that this occurs independently of dynamin activity. Our results indicate that RAB-5 promotes C. elegans embryonic polarity in both dynamin-dependent and -independent manners, by controlling PAR-6 localization and cortical dynamics through the regulation of its association with the cell cortex and the organization of the actin cytoskeleton

Etude du rôle de la vézatine, une protéine d' adhérence chez la souris (implication dans la différentiation épithéliale au cours du développement précoce et dans la spermatogenèse)

PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

The Small GTPase Ral orchestrates MVB biogenesis and exosome secretion

International audienceno abstrac

Extracellular Vesicles: Catching the Light in Zebrafish

International audienc

Mécanismes de division cellulaire asymétrique

Le processus de division cellulaire asymétrique aboutit à la génération de deux cellules filles aux caractéristiques différentes. Ce processus permet d’engendrer une diversité cellulaire nécessaire au bon développement des organismes pluricellulaires et joue également un rôle important dans l’autorenouvellement des cellules souches chez l’adulte. Les connaissances actuelles concernant les cellules souches cancéreuses suggèrent que la perte de l’asymétrie lors des divisions cellulaires peut mener à un excès de prolifération de cellules identiques et favoriser ainsi la tumorigenèse, ce qui souligne l’importance de décrypter les mécanismes menant à la division cellulaire asymétrique. Il existe deux voies possibles pour qu’une cellule se divise de façon asymétrique : soit l’asymétrie est dictée par l’environnement cellulaire proche (ou niche cellulaire), on parle alors de mécanisme extrinsèque, soit la cellule se polarise elle-même sans intervention extérieure, il s’agit alors d’un mécanisme intrinsèque à la cellule. Au cours des vingt dernières années, notre compréhension des mécanismes intrinsèques menant à la division cellulaire asymétrique a considérablement évolué grâce notamment à l’étude d’organismes modèles comme le nématode Caenorhabditis elegans et la mouche Drosophila melanogaster. Ces modèles ont permis de mettre en évidence des complexes moléculaires utilisés par la quasi-totalité des cellules se divisant de façon asymétrique et conservés jusque chez l’humain. Nous résumons ici les principaux mécanismes intrinsèques de la division cellulaire asymétrique décrits chez les organismes modèles et nous considérons la pertinence de ces modèles en regard du processus de tumorigenèse chez les mammifères

Influence de la mécanique des fluides sur la formation des métastases (Influence of fluid mechanics on metastasis formation)

Metastases are the main cause of cancer-related deaths. The chain of events leading to their development is called "the metastatic cascade". The biological and biochemical aspects of this process have been well studied but the importance of biomechanical parameters only recently became a focus in the field. Studies have shown the biological fluids (blood, lymph and interstitial fluid) to play a key role in the metastatic cascade. These fluids participate in the transport of circulating tumor cells (CTCs) as well as the factors that they secrete, while at the same time influencing the events of the metastatic cascade through the forces that they generate. The hemodynamic properties and topological constraints of the vascular architecture control the formation of metastatic niches and the metastatic potential of tumor cells. In this review, we discuss the importance of these mechanical forces and highlight the novel questions and research avenues that they open

Melt-Processed Anhydrous Proton Exchange Membranes for Fuel Cell Applications

Peer reviewed: NoNRC publication: Ye