An evolving understanding of sorting signals for endosomal retrieval

Summary: Complex mechanisms govern the sorting of membrane (cargo) proteins at endosomes to ensure that protein localization to the post-Golgi endomembrane system is accurately maintained. Endosomal retrieval complexes mediate sorting by recognizing specific motifs and signals in the cytoplasmic domains of cargo proteins transiting through endosomes. In this review, the recent progress in understanding the molecular mechanisms of how the retromer complex, in conjunction with sorting nexin (SNX) proteins, operates in cargo recognition and sorting is discussed. New data revealing the importance of different SNX proteins and detailing how post-translational modifications can modulate cargo sorting to respond to changes in the environment are highlighted along with the key role that endosomal protein sorting plays in SARS-CoV-2 infection.