To degrade or not to degrade: mechanisms and significance of endocytic recycling

Newly endocytosed integral cell surface proteins are typically either directed for degradation or subjected to recycling back to the plasma membrane. The sorting of integral cell surface proteins, including signalling receptors, nutrient transporters, ion channels, adhesion molecules and polarity markers, within the endolysosomal network for recycling is increasingly recognized as an essential feature in regulating the complexities of physiology at the cell, tissue and organism levels. Historically, endocytic recycling has been regarded as a relatively passive process, where the majority of internalized integral proteins are recycled via a nonspecific sequence-independent ‘bulk membrane flow’ pathway. Recent work has increasingly challenged this view. The discovery of sequence-specific sorting motifs and the identification of cargo adaptors and associated coat complexes have begun to uncover the highly orchestrated nature of endosomal cargo recycling, thereby providing new insight into the function and (patho)physiology of this process. Endocytosed membrane proteins can either be degraded in the lysosome or recycled back to the membrane. This decision, which has an impact on protein levels, spatial distribution and function, is controlled by recycling machineries at the endosome that recognize and segregate cargo destined for recycling, thereby preventing its degradation.