|STEP 1: Clathrin recruitment
Clathrin can be recruited to membranes by a variety of proteins including AP180, epsin, amphiphysin and adaptors. AP180 is illustrated here because this is a very efficient recruitment protein that binds to PiP2 in the plasma membrane and also induces the polymerisation of clathrin into a lattice (see AP180 pages).
|STEP 2/3: Clathrin polymerisation and Membrane Bending
The membrane is deformed with the aid of curvature driving molecules like epsin and amphiphysin. As illustrated for epsin, this protein dips into the membrane and displaces lip
ids in one leaflet and also binds to clathrin (see Epsin pages).
|STEP 3/2: Cargo and accessory protein recruitment
Adaptor proteins bind to cargo proteins and sequester these proteins into the forming clathrin bud. There are many different types of adaptor with different specificities (see Adaptors). Many of these
adaptors can also bind to other proteins via appendage domains. We call these proteins 'accessory proteins' (see comparison of appendage domains).
|STEP 4: Scission of vesicle from parent membrane
The large GTPase dynamin forms a helical collar around the neck of an invaginating clathrin-coated vesicle, where it may regulate, pinch or pop the vesicle from the parent membrane. We have shown that GTP hydrolysis is coupled to vesicle scission and that on GTP hydrolysis dynamin spirals undergo a length-wise extension in vitro- which we believe drives the vesicle away from the membrane causing lipid fission. (see Dynamin pages).