Objetivo The Melanoma Antigen (MAGE) genes received increasing attention due to their roles in human diseases, mainly cancer and neurodevelopmental disorders. The family includes over 25 genes in humans, characterized by a MAGE homology domain (MHD). TypeI subfamily contains 3 gene clusters, which are silent in normal tissues, except in male germ cells and placenta. TypeII subfamily contains un-clustered genes, expressed in embryonic and adult tissues, especially in the nervous system. TypeII proteins are involved in neuronal function and two of their members, Necdin and MAGEL2, are part of the locus that is invariably deleted in patients of the neurodevelopmental Prader Willi Syndrome. Yet, understanding their functional repertoire has been impeded in mammals by redundancy between the numerous members. We identified a unique homologue of the MAGE family in the nematode C. elegans, and named it MAGE-1. Our preliminary data indicate that MAGE-1 is a mitochondrial protein highly expressed in neurons and intestinal cells, and required for maintaining mitochondrial integrity and dynamics. Notably, re-examination of Necdin in the mouse revealed that it partially localizes to the inner membrane of mitochondria in neurons. In addition to identifying novel components regulating mitochondria in neurons, our findings suggest that mitochondrial dysfunction may underlie pathologies associated with loss of function of MAGE proteins. The proposal is structured around 3 aims: 1. Characterize the role of MAGE-1 in C. elegans; 2. Identify binding partners and signaling pathways of MAGE-1 in mitochondria; 3. Characterize the role, pathways and partners of Necdin in mitochondria of mammalian neurons. The expected results will enhance our understanding of the evolutionary relationships of MAGE genes, and will reveal and characterize novel functions for mammalian MAGE proteins, such as Necdin, providing fresh insight into the pathology of the associated neuronal diseases. Ámbito científico natural sciencesbiological sciencesneurobiologymedical and health sciencesclinical medicineoncologyskin cancermelanomanatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesclinical medicineobstetricsmedical and health sciencesbasic medicinepathology Programa(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Tema(s) FP7-PEOPLE-2013-IEF - Marie-Curie Action: "Intra-European fellowships for career development" Convocatoria de propuestas FP7-PEOPLE-2013-IEF Consulte otros proyectos de esta convocatoria Régimen de financiación MC-IEF - Intra-European Fellowships (IEF) Coordinador IDRYMA TECHNOLOGIAS KAI EREVNAS Aportación de la UE € 168 794,40 Dirección N PLASTIRA STR 100 70013 Irakleio Grecia Ver en el mapa Región Νησιά Αιγαίου Κρήτη Ηράκλειο Tipo de actividad Research Organisations Contacto administrativo Zinovia Papatheodorou (Ms.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos