Trends in Cell Biology
Volume 14, Issue 4, 1 April 2004, Pages 167-174
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Adaptable adaptors for coated vesicles

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Abstract

Adaptors select cargo for inclusion into coated vesicles in the late secretory and endocytic pathways. Although originally there were thought to be just two adaptors, AP-1 and AP-2, it is now clear that there are many more: two additional adaptor complexes, AP-3 and AP-4, which might function independently of clathrin; a family of monomeric adaptors, the GGAs; and an ever-growing number of cargo-specific adaptors. The adaptors are targeted to the appropriate membrane at least in part by interacting with phosphoinositides, and, once on the membrane, they form interconnected networks to get different types of cargo into the same vesicle. Adaptors participate in trafficking pathways shared by all cells, and they are also used to generate specialized organelles and to influence cell fate during development.

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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