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© Research

About

Imaging protein sorting and prions spreading

One of the most important properties of the epithelium is cell polarity, which results in the formation of distinct apical and basolateral domains of the plasma membrane. These distinct domains enable cells to perform their vectorial activities. The mechanisms responsible for the generation and maintenance of epithelial polarity have been only partially characterized. Elucidation of the molecular basis of cell polarity and of the mechanisms of intracellular trafficking is a fundamental goal in mammalian cell biology not only for the understanding of basic cell function but also because alteration of these processes are at the basis of many diseases.

The attention of the lab is focused on two major projects:

Project 1:  Mechanism of GPI-anchored protein sorting to the plasma membrane

Project 2: Intracellular and intercellular trafficking of the prion protein: the site of pathological conversion and the mechanism of spreading
 
In the first project, we are studying the mechanism of apical sorting of GPI-anchored proteins (GPI-APs) and the role of lipid microdomains (or rafts) and proteins and lipids segregation at the level of the Trans Golgi Network (TGN) in two model epithelial cell lines, MDCK and FRT cells, which have different sorting phenotypes.

In the second project, using these cells as well as neuronal cells, we are studying the intracellular and intercellular trafficking of PrPC, and its infectious form PrPSc (scrapie) which are also GPI-anchored.

These two projects are mutually supportive of each other and we combine a biochemical approach with different techniques of imaging in living cells. Furthermore, we are developing techniques to analyse the spatial organization of proteins and lipids in cellular membranes in order to understand how this is affecting the intracellular trafficking and sorting of GPI-APs. We are using similar approaches to understand the role of intracellular trafficking and of association to specific membrane domains in the function and in the pathological conversion of a specific cellular GPI-AP, the prion protein.

 

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Transversal Project

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25-28 Rue du Docteur Roux
75015, Paris
France