Obiettivo Protein trafficking is crucial to maintain organelle function and cellular homeostasis, and is regulated by sorting receptors. Sortilin is a membrane receptor that sorts proteins to the predisposed cellular compartments through both secretory and endocytic routes. To accomplish this function Sortilin is endowed with an ectodomain that binds a great variety of cargo proteins, and a cytosolic domain that recruits adaptor proteins to direct the receptor trafficking activities. In the last 15 years more than 20 cargo proteins of Sortilin have been identified leading to the discovery of key Sortilin functions related to lipoprotein metabolism, neurotrophic factor signaling and lysosomal trafficking. However, little is known about the specific mechanisms that regulate Sortilin intracellular trafficking and function, since few cytosolic adaptors, shared with other sorting receptors, have been identified. Based on this, the aim of the present project is to identify and characterize new cytosolic adaptors of Sortilin and shed light on these fundamental aspects. In particular, I will isolate, validate and characterize new adaptors and their binding sites, starting from the outcome of a large-scale analysis of candidate Sortilin adaptors performed by the host research group. To this aim I will use multiple techniques developed for the study of protein-protein interaction and cell biology. The results of this study will provide new knowledge about the Sortilin binding ability, intracellular trafficking and function. Importantly, elucidating the machinery and the molecular/regulatory mechanisms of protein trafficking is crucial to understand cellular physiology and pathology. In addition, since Sortilin is emerging as a major disease gene in cardiovascular, neurological, and neurodegenerative disorders, the results from the present project will provide new knowledge about the etiology of these complex diseases and propose novel therapeutic perspectives for their treatment. Campo scientifico natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomicsnatural sciencesbiological sciencescell biologymedical and health sciencesbasic medicinepathologymedical and health sciencesbasic medicinephysiologyhomeostasis Parole chiave SORT1 Programma(i) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Argomento(i) MSCA-IF-2014-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF) Invito a presentare proposte H2020-MSCA-IF-2014 Vedi altri progetti per questo bando Meccanismo di finanziamento MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF) Coordinatore AARHUS UNIVERSITET Contribution nette de l'UE € 212 194,80 Indirizzo NORDRE RINGGADE 1 8000 Aarhus C Danimarca Mostra sulla mappa Regione Danmark Midtjylland Østjylland Tipo di attività Higher or Secondary Education Establishments Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 212 194,80