Ubiquitin in trafficking: the network at work

Targeting of membrane proteins to their proper destination requires specific mechanisms. Protein cargos are included in vesicles that bud off a donor organelle and ultimately fuse with a target organelle, where the cargos are delivered. Endocytosis of transmembrane receptors (e.g., receptor tyrosine kinases, RTKs) follows a common scheme that consists of an internalization reaction and a delivery step, during which cargos are transferred to an endosomal station to be either directed to the lysosome for degradation or recycled back to the cell surface. At each stage along the endocytic route, short motifs within protein cargos and/or post-translational modifications regulate transmembrane receptor sorting. In recent years, studies have shown that ubiquitination acts as a signal for the internalization and sorting of plasma membrane proteins. Here, we present an overview of ubiquitin's role as a ‘signal’ for intracellular trafficking and give examples of the multifaced mechanisms of ubiquitin-regulated RTK endocytosis.