Estudio de la función molecular de las proteínas de la familia VPS13

  1. Tornero Écija, Alba Rocio
Dirigida por:
  1. Ricardo Escalante Hernández Director/a
  2. Vincent Olivier Director/a

Universidad de defensa: Universidad Autónoma de Madrid

Fecha de defensa: 24 de octubre de 2022

Tribunal:
  1. José Manuel Fuentes Rodríguez Presidente/a
  2. Miguel Fernández Moreno Secretario/a
  3. Luis Carlos Tábara Rodriguez Vocal
  4. Catalina Ribas Núñez Vocal
  5. Felipe Xosé Pimentel Muiños Vocal

Tipo: Tesis

Resumen

VPS13A is a lipid transfer protein located at different membrane contact sites (MCSs), whose mutation causes chorea-acanthocytosis (ChAc), a rare neurodegenerative disease for which there is no treatment at present. Previous studies showed the accumulation of endosomal and lysosomal markers in VPS13A-depleted HeLa cells, suggesting a defect in lysosomal degradation capacity and a partial autophagic dysfunction. In this thesis, we propose that therapeutic strategies aimed at modulating the endolysosomal pathway could be beneficial in the treatment of ChAc. We have established a CRISPR/Cas9 model in HeLa cells that allows studying the effects of the VPS13A alterations and the possible use of different compounds. In this model, a possible beneficial effect of rapamycin treatment was observed. Although new data has been generated in recent years related to VPS13A and its interacting proteins, there are still many questions unsolved about this protein that hampers the design of treatments for ChAc. In this thesis, we have further studied the subcellular localization of VPS13A and the identification of new adaptors. The VAB domain of VPS13A interacts with the protein SNX5, moreover both proteins can be part of the MCS between mitochondria and SNX5-containing endosomes