Endosomal Retrieval of Cargo: Retromer Is Not Alone.

Endosomes are major protein sorting stations in cells. Endosomally localised multi-protein complexes sort integral proteins, including signaling receptors, nutrient transporters, adhesion molecules, and lysosomal hydrolase receptors, for lysosomal degradation or conversely for retrieval and subsequent recycling to various membrane compartments. Correct endosomal sorting of these proteins is essential for maintaining cellular homeostasis, with defects in endosomal sorting implicated in various human pathologies including neurodegenerative disorders. Retromer, an ancient multi-protein complex, is essential for the retrieval and recycling of hundreds of transmembrane proteins. While retromer is a major player in endosomal retrieval and recycling, several studies have recently identified retrieval mechanisms that are independent of retromer. Here, we review endosomal retrieval complexes, with a focus on recently discovered retromer-independent mechanisms.