Module 4: Figure endocytosis

Control of clathrin-mediated endocytosis.

The uptake of plasma membrane proteins by the process of endocytosis is regulated by two main mechanisms. First, the adaptor protein 2 (AP2) is phosphorylated by adaptor-associated kinase 1 (AAK1), which helps it to bind to cargo proteins such as the transferrin receptor (TFR). Secondly, the PtdIns4P 5-kinase γ (PIPKIγ) phosphorylates PtdIns4P to PtdIns4,5P2, which contributes to the binding of cargo. As the AP2–TFR complexes aggregate, they begin to bind clathrin and the membrane starts to invaginate. Various proteins, which bind to the neck region, are responsible for the process of scission during which the vesicle is budded off into the cytoplasm. Dephosphorylation of AP2 and PtdIns4,5P2 by protein phosphatases and synaptojanin-1 (SJ1) respectively result in disassembly of the coat components that are re-used for further rounds of endocytosis.