Retromer‐mediated endosomal protein sorting: The role of unstructured domains

Abstract The retromer complex is a key element of the endosomal protein sorting machinery that is conserved through evolution and has been shown to play a role in diseases such as Alzheimer’s disease and Parkinson’s disease. Through sorting various membrane proteins (cargo), the function of retromer complex has been linked to physiological processes such as lysosome biogenesis, autophagy, down regulation of signalling receptors and cell spreading. The cargo-selective trimer of retromer recognises membrane proteins and sorts them into two distinct pathways; endosome-to-Golgi retrieval and endosome-to-cell surface recycling and additionally the cargo-selective trimer functions as a hub to recruit accessory proteins to endosomes where they may regulate and/or facilitate retromer-mediated endosomal proteins sorting. Unstructured domains present in cargo proteins or accessory factors play key roles in both these aspects of retromer function and will be discussed in this review.