Responsable: Manuel Muñiz Guinea
Tipo de Proyecto/Ayuda: Plan Nacional del 2005
Referencia: BFU2005-01642
Fecha de Inicio: 31-12-2005
Fecha de Finalización: 31-12-2008

Empresa/Organismo financiador/es:

• Ministerio de Educación y Ciencia

Equipo:

• Otros Investigadores:
  • María Auxiliadora Aguilera Romero

Resumen del proyecto:

Protein sorting events taking place at the early secretory pathway are essential for eukaryotic cell physiology. They allow selective exit of secretory proteins from the endoplasmic reticulum (ER), maintain efficient retention of endogenous ER components, prevent misfolded proteins escaped to the Golgi from moving forward along the secretory pathway, and support recycling of transport factors required to mediated further rounds of anterograde traffic. A conserved group of integral membrane proteins, referred to as the p24 family, are thought to act in concert with COPII and COPI coats to sort proteins during transport through the early secretory pathway. p24 proteins are assembled into heteromeric complexes that continuously cycle between ER and Golgi compartments. Our data suggest that p24 complex might act as a cargo receptor concentrating specific proteins into both COPII and COPI vesicles, to be efficiently exported to the Golgi or retrieved to the ER respectively. The aim of this proposal is to analyse the exact role played by p24 complex in protein sorting during bidirectional transport between ER and Golgi using the yeast Saccharomyces cerevisiae as a cell-model system. We will start performing a genetic analysis to study functional interactions among p24 proteins and transport machinery components. An in vitro ER budding assay will be used to study the role of p24 complex in protein sorting upon ER exit. In parallel, by using an in vitro Golgi budding assay we will test directly the putative role of p24 complex in protein cargo packaging into COPI vesicles. In addition, this assay will allow us to address the existence of different return routes to the ER. Finally, the role of p24 complex in misfolded proteins sorting during the ER associated quality control system will be investigated. It is our hope that this study will allow us to better understand the operation of protein sorting mechanisms at the early secretory pathway.