Figure 7
Model for endocytic pit initiation. (a) In the `locked', cytosolic state, both clathrin and cargo binding by AP2 is autoinhibited. Recruitment to the plasma membrane (horizontal grey line) by interactions with PtdIns(4,5)P2 (black spheres) stimulates a conformational change in AP2 (light grey) that reveals both the binding sites for cargo-peptide motifs (yellow/orange lines) and the clathrin-binding epitope (red bar). Binding both clathrin and cargo stabilizes AP2 in the `open' conformational state. (b) Once stabilized on the membrane, AP2 binds and recruits further clathrin (dark grey), stimulating clathrin polymerization. (c) Polymerized clathrin, with the assistance of other factors (Miller et al., 2015), deforms the membrane to produce a curved clathrin-coated `bud' that ultimately undergoes scission to produce a mature transport vesicle. |