Objectif The endoplasmic reticulum (ER) is the largest intracellular organelle of mammalian cells. It fulfills major functions such as folding and quality control of membrane proteins, lipid biosynthesis, calcium storage, and modulation of apoptosis. This diversity of functions is accompanied by a complex 3D architecture, the maintenance of which is essential, since alterations lead to disease. How this architecture is generated, how proteins localize to specific subdomains and how structure and functions are coordinated is poorly understood. Our unpublished observations show that many ER membrane proteins, involved in key functions or in organelle shaping, are lipid modified, by the same palmitoyltransferases, and in a switch-like manner. We hypothesize that palmitoyltransferases act as regulators of the mammalian ER, controlling the function of a network of key proteins through reversible acylation, analogous to the control of signaling networks by phosphorylation. To establish the role of palmitoylation in coordinating ER structure/function, we propose a program integrating biochemical, functional and modeling approaches. We will determine the ER palmitome and investigate the impact of acylation on the function of individual proteins, on ER architecture and on the ER lipidome. We will analyze the interplay between and ubiquitination in controlling ER functions. Since we found that the DHHC6 palmitoytransferase is essential in mice and palmitoylates key ER proteins, we will study this enzyme in depth in terms of structure, function, target specific and regulation. Finally, we will combine the information emanating from these studies into a mathematical model of the ER palmitoylation network. Champ scientifique natural scienceschemical sciencesinorganic chemistryalkaline earth metalsnatural sciencesbiological sciencesbiochemistrybiomoleculeslipidsnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymesnatural sciencesmathematicsapplied mathematicsmathematical model Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) ERC-AG-LS3 - ERC Advanced Grant - Cellular and Developmental Biology Appel à propositions ERC-2013-ADG Voir d’autres projets de cet appel Régime de financement ERC-AG - ERC Advanced Grant Institution d’accueil ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE Contribution de l’UE € 2 443 949,00 Adresse BATIMENT CE 3316 STATION 1 1015 Lausanne Suisse Voir sur la carte Région Schweiz/Suisse/Svizzera Région lémanique Vaud Type d’activité Higher or Secondary Education Establishments Contact administratif Caroline Vandevyver (Dr.) Chercheur principal Francoise Gisou Van Der Goot (Prof.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée Bénéficiaires (1) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE Suisse Contribution de l’UE € 2 443 949,00 Adresse BATIMENT CE 3316 STATION 1 1015 Lausanne Voir sur la carte Région Schweiz/Suisse/Svizzera Région lémanique Vaud Type d’activité Higher or Secondary Education Establishments Contact administratif Caroline Vandevyver (Dr.) Chercheur principal Francoise Gisou Van Der Goot (Prof.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée
