Retrieval of endosomal cargo via protein scaffolds
Ponente: Aitor Hierro
CIC bioGUNE [Vizcaya]
Host: José María De Pereda
Salón de actos del Centro de Investigación del Cáncer
Recycling prevents waste, reduces consumption and saves energy. Living cells constantly recycle proteins and lipids, with a direct impact on nutrient uptake, re-sensitisation to environmental signals, immune surveillance and waste management. Endosomes are key intracellular recycling compartments where the biosynthetic and endocytic pathways intersect. Here, the fate of sorting receptors is directly linked to their selective recruitment into tubulo-vesicular carriers. Retromer is a multiprotein complex that assembles on endosomes and forms tubular vesicles that return specific integral membrane proteins to a variety of cellular compartments. Retromer's cargo includes signalling receptors, ion channels, nutrient transporters and enzymes that are essential for a wide range of physiological processes. Nonetheless, our understanding of the mechanisms that regulate the recruitment of retromer to endosomes, the concentration of cargo in prebudding domains and the coordinated assembly of the tubular coat remains very limited. Spatiotemporal control of these events not only is essential for general proteostasis and neuroprotection, but also is subverted by numerous pathogens. The seminar will summarize the current structural, functional and mechanistic models together with recent findings from the research group.