Responsable: Manuel Muñiz Guinea
Tipo de Proyecto/Ayuda: Plan Nacional del 2011
Referencia: BFU2011-24513
Fecha de Inicio: 01-01-2012
Fecha de Finalización: 31-12-2012

Empresa/Organismo financiador/es:

• Ministerio de Ciencia e Innovación

Equipo:

• Investigadores:
  • Javier Manzano López
  • María Esther Martín Rubio

Resumen del proyecto:

Vesicular transport through the eukaryotic secretory pathway is essential for cellular function and multicellular development. This evolutionary conserved process depends on cytosolic coat protein complexes that form vesicles, select specific cargo molecules for incorporation into the vesicles and direct the vesicles to their correct intracellular destination. Two types of coats operate in the early secretory pathway: COPII mediates the export from the endoplasmic reticulum (ER), while COPI is involved in the retrograde transport from the Golgi to the ER and between Golgi cisternae. Unfortunately, the mechanisms that regulate the functional activity of these coats are poorly understood. During the last few years we have obtained evidence indicating that a conserved group of integral membrane proteins, referred to as the p24 family, controls coat activity within the early secretory pathway. p24 proteins are assembled into heteromeric complexes that continuously cycle between ER and Golgi compartments. Our data suggest that the p24 complex might acts as “professional” coat protein binder that regulates multiple vesicular trafficking events by recruiting and stabilizing COPII and COPI coats to the ER and Golgi membranes respectively. The aim of this proposal is to investigate the precise molecular mechanisms by which the p24 complex operates at the ER/Golgi interface using the yeast Saccharomyces cerevisiae as a cell-model system. We will address these points: 1) The regulatory mechanisms by which the p24 complex couples luminal cargo recognition with COPII vesicle biogenesis 2) The central role of the p24 complex in COPI vesicle generation from the Golgi membrane. 3) The modulation of vesicle tethering events by the p24 complex at the ER/Golgi interface. This study will reveal basic mechanisms underlying an essential biological process such as the vesicular trafficking in the early secretory pathway.