Identification and characterization of new cytosolic ligands of Sortilin

Project Information

SORT1LIG

Grant agreement ID: 660980

DOI

10.3030/660980

Project terminated on 31 March 2016

EC signature date 11 March 2015

Start date 1 January 2016

End date 31 December 2017

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 212 194,80

EU contribution

€ 212 194,80

Coordinated by

AARHUS UNIVERSITET
Denmark

Periodic Reporting for period 1 - SORT1LIG (Identification and characterization of new cytosolic ligands of Sortilin)

Reporting period: 2016-01-01 to 2017-12-31

Summary of the context and overall objectives of the project

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. To accomplish this function Sortilin is endowed with an ectodomain that binds to a great variety of cargo proteins, and a cytosolic domain that recruits adaptor proteins which control its 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, still little is known about the specific mechanisms that regulate Sortilin intracellular trafficking and function, since few cytosolic adaptors 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 Notably, 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.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

The work perfomed during the duration of the action (3 months) was mainly focused on the expression analysis of Sortilin and of a candidate cytosolic adaptor in cell lines and in brain tissue homogenates. The results achieved allowed to identify two cell lines and two brain tissues co-expressing Sortilin and the canditate adaptor. These tools would be useful for future studies focused on the validation and characterization of their interaction.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

Not applicable