Responsable: Manuel Muñiz Guinea
Tipo de Proyecto/Ayuda: Proyectos de Excelencia de la Junta de Andalucía
Referencia: P09-CVI-4503
Fecha de Inicio: 03-03-2011
Fecha de Finalización: 03-03-2015

Empresa/Organismo financiador/es:

• Junta de Andalucía (Consejería de Innovación, Ciencia y Empresas)

Equipo:

• Investigadores:
  • Antonio José Caruz Arcos
  • Veit Goder
• Otros Investigadores:
  • María Auxiliadora Aguilera Romero
  • Javier Manzano López
  • Nuria Urda Garrido

Resumen del proyecto:

GPI-proteins are molecules that have a soluble protein portion attached to the membrane by a glycosylphosphatidylinositol (GPI) anchor. These proteins are almost exclusively found at the plasma membrane of all eukaryotic cells, where they play a variety of physiological roles. They include signal transduction, cell–cell interaction, cell adhesion, host defense and cell wall biosynthesis. It is therefore not surprising that GPI-proteins are also directly involved in a number of human pathologies like infectious diseases (for example, malaria, AIDS, prion-based diseases and Candida albicans infection), genetic disorders (for example, paroxysmal nocturnal hemoglobinuria) and cancer. Despite this importance, key steps in GPI-protein biosynthesis are only very poorly understood. GPI-proteins are initially assembled in the endoplasmic reticulum (ER). However, due to their special membrane anchor, they do not utilize the machinery for ER quality control, folding and subsequent export, like “conventional” membrane proteins. Instead, they require distinct mechanisms, most of them currently being unknown. The main aim of this project is to elucidate the molecular machineries and the principles that the eukaryotic cell uses to ensure that GPI-proteins are correctly folded and transported to the cellular plasma membrane. The results of our studies should help unravel an essential biological process and provide molecular insight into several diseases linked to GPI-proteins. Importantly for this proposal, we will also directly address the specific roles of human GPI-proteins for HIV infection and cancer progression.