| Protein trafficking and Degradation |
Molecular mechanisms involved in the process of autophagy
Key words: Autophagy, VMP1, VPS13, WIPI, BPAN, Chorea-acanthocytosis, Saccharomyces cerevisiae
Our main goal is to characterize molecular mechanisms that control protein trafficking and degradation, and are potentially involved in human diseases.
In the past years, we have studied the regulatory mechanisms of arrestin-related proteins that function as endocytic adaptors for receptors and transporters at the plasma membrane.
More recently, we started a project to characterize the function of VMP1, VPS13 and WIPI proteins in the process of autophagy.
Autophagy is an intracellular degradation mechanism involved in several pathologies such as neurodegenerative diseases ChAc (Corea-acanthocytosis) and BPAN (Beta-propeller Protein-Associated Neurodegeneration). Mutations in the VPS13A and WIPI4/WDR45 genes are responsible for these diseases.
We aim to determine the function of these proteins in autophagy. VPS13 and WIPI proteins are evolutionarily conserved and we use the model organism S. cerevisiae to analyze their function and to identify their interactome by using the two-hybrid system.
The specific goals are:
- Identification of new VMP1 and VPS13 interactors and analysis of their possible role in lipid trafficking
- Characterization of the molecular mechanisms involved in WIPI-mediated recruitment of the autophagic machinery to the autophagosomal membrane
- Functional analysis of a new Atg2 interactor potentially involved in autophagy
- Generation by CRISPR/Cas9 genome editing and characterization of WIPI KOs in HeLa cells