clathrinadaptor

Clathrin adaptor proteins are cytosolic multiprotein complexes that recruit clathrin during vesicle budding and thereby couple membrane cargo selection to vesicle formation. They operate in various trafficking routes, notably endocytosis at the plasma membrane and delivery from the trans-Golgi network to endosomes and lysosomes. By selecting cargo and organizing clathrin coats, they help shape the clathrin-coated vesicle system that maintains intracellular protein sorting.

The best characterized clathrin adaptors are adaptor protein complexes AP-1, AP-2, AP-3 and AP-4, with AP-5 described more recently. Each AP complex is a heterotetramer of two large adaptins, one mu subunit, and one sigma subunit. They assemble on donor membranes and recruit clathrin to form coated vesicles.

Cargo recognition: The mu subunits bind sorting motifs such as YxxΦ in cargo tails, while other subunits recognize dileucine-type signals. This enables receptors and transporters to be selectively packaged into clathrin-coated vesicles. Adaptor complexes also interact with ARF GTPases and with accessory factors that promote budding.

Localization and function: AP-2 operates at the plasma membrane to drive endocytosis; AP-1 functions at the trans-Golgi network and endosomes; AP-3 and AP-4 participate in endolysosomal trafficking; AP-5 is linked to late endosome pathways but is less well defined. Additional clathrin adaptors include GGAs, which function at the Golgi and endosomes.

Clinical relevance: Mutations in clathrin adaptor subunits can cause human disease; for example AP-3 defects underlie Hermansky-Pudlak syndrome type 2, and AP-4 deficiency is associated with neurodevelopmental disorders, illustrating the essential role of clathrin-mediated trafficking in physiology.