Trends in Cell Biology
Adaptable adaptors for coated vesicles
Section snippets
Types of adaptors
The first coated vesicle adaptors to be identified were the AP-1 and AP-2 complexes. Both of these adaptors are highly enriched in purified clathrin-coated vesicles, second in abundance only to clathrin itself, and they both promote clathrin assembly in vitro. (The name AP was originally introduced as an acronym for assembly polypeptides [1], although conveniently it also stands for ‘adaptor protein’.) AP-1 and AP-2 are heterotetramers and contain related sets of subunits (γ, β1, μ1 and σ1 in
Getting adaptors onto the right membrane
At one time, it was generally assumed that adaptors were recruited onto membranes by binding to the proteins that would end up as cargo in the coated vesicle. The problem with this idea was that, if the adaptors were doing their job efficiently, then the cargo proteins ought to be more concentrated in the acceptor membrane than in the donor membrane, yet the adaptors are always recruited onto the donor membrane.
The first indication that adaptor recruitment might be more complicated than a
Cargo selection
By far the best-characterized adaptor–cargo interaction is the one between the μ subunits of AP complexes and the sorting signal YXXΦ (where Φ is a bulky hydrophobic residue). This signal can act both as an internalization signal at the plasma membrane (e.g. in the transferrin receptor) and as an intracellular sorting signal (e.g. in lysosomal membrane proteins such as LAMP-1). The YXXΦ–μ interaction was first identified in a yeast two-hybrid library screen, in which μ2 was picked out of ∼2.5×10
Adaptor interaction networks
The finding that not only AP-2 but also some of the cargo-specific adaptors can interact with PIP2, cargo proteins and clathrin suggests that these other proteins might in fact be just as good as AP-2 at supporting clathrin-mediated endocytosis. Certainly some unicellular organisms seem to manage very well without AP-2. In the budding yeast S. cerevisiae, there is an AP-2-related complex that localizes to the plasma membrane [52]; however, knocking out AP-2 has no apparent effect on
Adapting adaptors for specific pathways
One important difference between COP coats and adaptor/clathrin coats is that, whereas COPI and COPII are essential for cell viability, in most cases single cells can get by without individual adaptors, and even without clathrin. The discovery in 1985 that clathrin knockouts in yeast were viable [73] was initially greeted with some dismay, because it seemed to suggest that clathrin was relatively unimportant. However, both clathrin and adaptors are very highly conserved proteins, and it is
Concluding remarks
Thus, although ten years ago there were thought to be only two adaptors – AP-1 and AP-2 – we now know that adaptors are a diverse collection of proteins with similar functions in cargo sorting. Different types of adaptors can act together on the same membrane to co-recruit cargo into the same population of vesicles, and related adaptors can act on different membranes – or even on the same membrane – to recruit cargo into different populations of vesicles. The docking of adaptors onto membranes
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