Living cells constantly recycle receptors, proteins and lipids with a direct impact on nutrient uptake, re-sensitisation to environmental signals, immune surveillance and waste management. Failure to recycle results in reduced signalling, oxidative stress, protein mislocalisation and aggregation, which are pathological hallmarks of many cardiovascular, cancer, and neurodegenerative diseases. Endosomes are key 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. Our understanding of receptor recycling in a motif-dependent manner, the formation of such tubulo-vesicles and the functional components defining their architecture remains very limited. Retromer is a novel protein coat complex with a central role in multiple receptor-sorting events in the endosomes. Retromer combines receptor recruitment with membrane tubulation properties, but unlike other classical coats, it does so through a single-layer or “cage-free” organization.
This laboratory is interested in understanding how retromer components form a coat around tubulo-vesicles, how transmembrane receptors are selectively recruited to control essential cell processes, and how certain pathogens subvert and co-opt these interactions.