Endocytic sorting of transmembrane protein cargo

The accurate distribution and recycling of transmembrane proteins amongst the membrane-bound organelles of the cell is vital to ensure its correct functioning. Transmembrane protein cargo destined for clathrin-mediated endocytosis and transport along the endocytic pathway is sorted into transport vesicles by interactions with adaptors, which simultaneously link clathrin to the membrane. Clathrin adaptors recognize a variety of signals present in the cytoplasmic portions of cargo proteins; recent structural, biophysical and cell biological studies have elucidated new types of cargo-adaptor interactions and probed the molecular mechanisms regulating cargo selection and vesicle maturation. Here, we review this recent progress in the context of our existing knowledge of endocytic sorting mechanisms.

► Recognition of sorting signals by clathrin adaptors is reviewed.
► New modes of adaptor-signal recognition have been discovered.
► Preference for poly-ubiquitination versus mono-ubiquitination has been explored structurally.
► New regulatory mechanisms have been elucidated.