Adaptins

Adaptins are a family of adaptor protein complexes that mediate clathrin-coated vesicle formation by selecting cargo proteins and recruiting the clathrin coat. In most cells, adaptins function as part of heterotetrameric AP complexes, including AP-1, AP-2, AP-3, AP-4 and AP-5. Each complex is built from two large subunits and two smaller subunits, a medium mu and a small sigma. Different AP complexes localize to distinct membranes: AP-2 operates at the plasma membrane, while AP-1, AP-3, AP-4 and AP-5 act at the trans-Golgi network or endosomal compartments.

Cargo recognition is a key feature of adaptins. The mu subunit of adaptins recognizes sorting signals on cargo proteins, such as tyrosine-based and dileucine motifs, enabling selective packaging into clathrin-coated vesicles. The sigma subunits help stabilize the complex and aid in coat assembly, while the large adaptin subunits interact with clathrin and accessory factors to sculpt vesicles.

Membrane recruitment of AP-2 to the plasma membrane is facilitated by phosphoinositide PI(4,5)P2, whereas several AP complexes are recruited to intracellular membranes by ARF family GTPases. Through their coordinated actions, adaptins couple cargo selection to vesicle formation, controlling traffic between the plasma membrane, endosomes, and the trans-Golgi network.

Clinical relevance is noted in humans. Mutations affecting AP-4 subunits cause AP-4 deficiency syndrome, with neurodevelopmental problems. AP-3 mutations are linked to Hermansky-Pudlak syndrome type 2, a disorder of lysosome-related organelle biogenesis. Adaptins are evolutionarily conserved and essential for proper intracellular trafficking.