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 subject 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 endo-lysosomal network for recycling is increasingly recognised as an essential feature in regulating the complexities of cell, tissue and organism-level physiology. Historically, endocytic recycling has been regarded as a relatively passive process, where the majority of internalized integral proteins are recycled via an unspecific 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 has begun to uncover the highly orchestrated nature of endosomal cargo recycling, thereby providing new insight into the function and (patho)physiology of this process.