Machinery, motifs and mechanisms of endosome-to-Golgi retrieval.

Every cell in the body runs a protein-sorting operation that, when it fails, can strand vital proteins in the wrong compartment and trigger diseases like Alzheimer’s. Cells are packed with specialised compartments—the nucleus holds DNA, others handle waste or build proteins. To get the right protein to the right place, cells use short molecular “tickets” on each protein and “ticket inspectors” that read those tickets and direct the protein into the correct carrier. This project focuses on one specific sorting route: the retrieval pathway that pulls proteins back from the endosome to the Golgi apparatus. When this retrieval fails, proteins meant for other compartments end up stuck or degraded, and that misrouting is linked to neurodegeneration. The researchers will map all the “ticket inspectors” (the proteins that recognise retrieval signals) and identify the exact “tickets” (the molecular motifs) required for a protein to be pulled back along this route. This is fundamental cell biology—there is no immediate medical treatment or diagnostic tool coming from this work. But understanding the basic sorting machinery is essential. Similar fundamental studies of intracellular transport have already revealed how cholesterol trafficking fails in Niemann-Pick disease and how viruses hijack cellular routes to infect cells. A complete map of this retrieval pathway could eventually point to new targets for drugs that correct protein misrouting in Alzheimer’s and related disorders.