Cargo adaptors

Cargo Adaptors are the proteins that link cargo into the clathrin-coated pit. Adaptors can also be used to refer to the subset of protein which we call 'accessory proteins' (the protein used in CCV formation that do not bind to cargo).

There are 2 main types of adaptor molecules:
Classical adaptors: AP1, AP2, AP3 and AP4 tetrameric adaptor complexes (see below).
Alternative adaptors: a single protein (in some cases homodimers) that links cargo into clathrin-coated pits. Examples are GGAs, epsins, Hrs and disabled2. Some of these protein can al so bind to accessory proteins.

Accessory proteins: Clathrin recruitment, membrane bending and scission molecules etc. This can cover all proteins involved in clathrin-mediated endocytosis except clathrin. But the definition is more usefully applied when it neither covers clathrin nor cargo adaptors.

AP2 adaptor protein complex Accessory protein recruitment by AP2 adaptors
Classical adaptors: e.g. the AP2 adaptor complex

There are 4 different subunits (as illustrated in the model above based on the crystal structure) and thus they are sometimes called polymeric or hetrotetrameric adaptors. The trunk domain binds to membranes and to cargo via the mu and beta subunits. The appendage domains (sometimes called Ears) bind to accessory proteins. Structures of a number of appendage domains have been solved and binding motifs and partners characterised (see appendages). The hinge domains bind to clathrin terminal domains. AP1, AP3 and AP4 adaptors have similar subunit compositions and bind to different cargo and accessory proteins (see Adaptor table 1).

For further information on cargo binding motifs, see Adaptor table 1.

The AP2 adaptor complex works on the plasma membrane to internalise cargo (see CCV assembly). In the above picture the beta-append age is bound to the clathrin cage while the alpha-appendage is free to recruit accessory proteins. The AP2 complex is important in synaptic vesicle recycling, and thus brain homogenates are a common source of material for biochemical experiments.
Subunits of AP adaptor complexes GGAs, alternative cargo adaptors
Other AP complexes

There is significant homology between subunits of similar colours. Note that the gamma appendage domain in the AP1 complex has only one subdomain like the GGA appendage domain in the next panel.
AP1 complex: cargo selection from the TGN and endosomes
AP2 complex: cargo selection from plasma membrane
AP3 complex: cargo selection to lysosomes
AP4 complex: ??

GGAs: an Alternative Clathrin Cargo-adaptor

There are now a number of different 'alternative' cargo adaptors. These include the GGAs, Hrs, arrestins and epsins. These proteins are discussed in the coming pages.

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