ER-to-Golgi trafficking of procollagen in the absence of large carriers

AbstractSecretion and assembly of collagen is fundamental to the function of the extracellular matrix. Defects in the assembly of a collagen matrix lead to pathologies including fibrosis and osteogenesis imperfecta. Owing to the size of fibril-forming procollagen molecules it is assumed that they are transported from the endoplasmic reticulum to the Golgi in specialised large COPII-dependent carriers. Here, analysing endogenous procollagen and a new engineered GFP-tagged form, we show that transport to the Golgi occurs in the absence of large carriers. Large GFP-positive structures are observed occasionally but these are non-dynamic, are not COPII-positive, and label with markers of the ER. We propose a “short-loop” model of COPII-dependent ER-to-Golgi traffic that, while consistent with models of ERGIC-dependent expansion of COPII carriers, does not invoke long-range trafficking of large vesicular structures. Our findings provide an important insight into the process of procollagen trafficking and reveal a short-loop pathway from the ER to the Golgi, without the use of large carriers.SummaryTrafficking of procollagen is essential for normal cell function. Here, imaging of GFP-tagged type I procollagen reveals that it is transported from the endoplasmic reticulum to the Golgi, without the use of large carriers.</jats:sec

Mise en place d'un programme d'assurance qualité pour la prise en charge de la douleur aiguë dans les services de la fédération de l'appareil locomoteur du CHU de Nancy

NANCY1-SCD Medecine (545472101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Morphodynamisme des rivières (sélection de largueur, rides et dunes)

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

Dense snow flowing past a deflecting obstacle: An experimental investigation

International audienceDense snow flowing down a rough inclined chute and interacting with a deflecting obstacle is experimentally investigated. These experiments are of considerable practical interest for the design of deflecting dams that are built to defend against large-scale snow avalanches. Our study focused on the maximum run-up reached by the dense flowing snow on a deflector. It was found that the maximum run-up was strongly correlated to the upstream Froude number and the deflecting angle of the obstacle. The data was compared with the predictions from a simple conversion of kinetic energy to potential energy on one hand and with oblique shock calculations on the other hand. The predicted values from the first approach were in better agreement with the measured values in comparison with the second approach. During a short transient phase at the end of the flow, it was shown that the flow features from our snow experiments were identical to the flow features from the previous granular and water experiments. In these conditions, the shallow-layer theory was also found to be relevant for snow flows

Local Secretory Trafficking Pathways in Neurons and the Role of Dendritic Golgi Outposts in Different Cell Models

A fundamental characteristic of neurons is the relationship between the architecture of the polarized neuron and synaptic transmission between neurons. Intracellular membrane trafficking is paramount to establish and maintain neuronal structure; perturbation in trafficking results in defects in neurodevelopment and neurological disorders. Given the physical distance from the cell body to the distal sites of the axon and dendrites, transport of newly synthesized membrane proteins from the central cell body to their functional destination at remote, distal sites represents a conundrum. With the identification of secretory organelles in dendrites, including endoplasmic reticulum (ER) and Golgi outposts (GOs), recent studies have proposed local protein synthesis and trafficking distinct from the conventional anterograde transport pathways of the cell body. A variety of different model organisms, including Drosophila, zebrafish, and rodents, have been used to probe the organization and function of the local neuronal secretory network. Here, we review the evidence for local secretory trafficking pathways in dendrites in a variety of cell-based neuronal systems and discuss both the similarities and differences in the organization and role of the local secretory organelles, especially the GOs. In addition, we identify the gaps in the current knowledge and the potential advances using human induced pluripotent stem cells (iPSCs) in defining local membrane protein trafficking in human neurons and in understanding the molecular basis of neurological diseases

Synthèse de CF -carbasucres par cyclisation radicalaire et application à la synthèse d'analogues de glycoconjugués à visée thérapeutique

Les O-glycoconjugués et les dérivés glycosidiques sont des composés naturels impliqués dans de nombreux processus biologiques. Cependant, leurs propriétés sont grevées par la médiocre stabilité in vivo de la liaison osidique. Il est donc intéressant de développer des mimes non hydrolysables. Nous nous sommes intéressés au remplacement de l oxygène intracyclique par un groupement gem-difluorométhylène.La synthèse d analogues difluorocarbocycliques de 5-désoxypentofuranoses et de 1-amino-5-désoxypentofuranoses a été décrite. La synthèse comporte une addition dePhSeCF2TMS sur des aldéhydes dérivés de sucres ou sur les tert-butanesulfinylimines correspondantes, suivie d une cyclisation radicalaire. La diastéréosélectivité de ces deux étapes-clés a été étudiée, puis cette stratégie de synthèse a été appliquée à la synthèse deCF2-carbasucres, notamment l analogue CF2-carbocyclique du D-arabinose.O-Glycoconjugates and carbohydrate-based molecules are natural compoundsimplied in many biological processes. However, their properties are burdened by the low invivo stability of the osidic bond. It is thus interesting to develop non hydrolyzable mimetics.We were interested in the replacement of the intracyclic oxygen by a gem-difluoromethylenegroup.The synthesis of difluorinated carbocyclic analogues of 5-deoxypentofuranoses and1-amino-5-deoxypentofuranoses is described. The sequence involves an addition ofPhSeCF2TMS to carbohydrate-derived aldehydes or their corresponding tertbutanesulfinyliminesfollowed by a radical cyclization. The stereochemical outcome of these two key steps was studied, and then this strategy was applied to CF2-carbasugars, inparticular of the CF2-carbocyclic analogue of D-arabinose.ROUEN-INSA Madrillet (765752301) / SudocSudocFranceF

Dense snow flowing past a deflecting obstacle: An experimental investigation

International audienceDense snow flowing down a rough inclined chute and interacting with a deflecting obstacle is experimentally investigated. These experiments are of considerable practical interest for the design of deflecting dams that are built to defend against large-scale snow avalanches. Our study focused on the maximum run-up reached by the dense flowing snow on a deflector. It was found that the maximum run-up was strongly correlated to the upstream Froude number and the deflecting angle of the obstacle. The data was compared with the predictions from a simple conversion of kinetic energy to potential energy on one hand and with oblique shock calculations on the other hand. The predicted values from the first approach were in better agreement with the measured values in comparison with the second approach. During a short transient phase at the end of the flow, it was shown that the flow features from our snow experiments were identical to the flow features from the previous granular and water experiments. In these conditions, the shallow-layer theory was also found to be relevant for snow flows