Endocytosis and signalling: intertwining molecular networks

Abstract

Signalling receptors are rapidly endocytosed following activation and then move through a series of endosomal compartments. A common property of signalling receptor endocytosis is the efficient sorting of receptors for lysosomal degradation, which is mediated by their ubiquitylation and sorting into intraluminal vesicles of multivesicular bodies. Endocytosis attenuates signalling that is triggered from the plasma membrane by decreasing the number of receptors available to extracellular ligands and by segregating activated receptors from plasma membrane effectors and substrates. Many types of receptor remain active in endosomes and interact with downstream effectors, which allows them to continue signalling after internalization. In neuronal cells, endosomes containing active complexes of neurotrophin receptors are transported from axonal termini to the cell soma to support retrograde survival signalling. Assembly of signalling complexes on the basis of endosome-specific components allows endosome-specific signalling to occur. Activation of signalling receptors leads to modifications of the basic endocytic machinery and contributes to the receptor-specific changes in endocytic processes. The traditional duality of signalling and endocytosis as two independent processes is beginning to give way to a view that these cellular processes are based on intertwining molecular networks.