adaptin

Adaptin is a family of adaptor protein complexes that mediate the formation of clathrin-coated vesicles in eukaryotic cells. They function as heterotetrameric assemblies that connect cargo receptors on membranes to the clathrin coat, enabling cargo selection and vesicle budding during intracellular trafficking.

There are five known adaptor protein complexes: AP-1, AP-2, AP-3, AP-4, and AP-5. Each complex comprises four subunits: two large adaptin subunits, one medium subunit (mu), and one small subunit (sigma). The specific subunits and their arrangement determine the membrane site and cargo set for the complex. AP-2 operates mainly at the plasma membrane and drives clathrin-mediated endocytosis; AP-1 and AP-3 function at the trans-Golgi network and endosomal/lysosomal pathways; AP-4 participates in Golgi-to-endosome trafficking; AP-5 is less well characterized but is implicated in late endosome/lysosome function.

Function and mechanism: Adaptins recognize sorting signals in cargo proteins (for example YXXΦ and dileucine motifs) via their mu subunits, and recruit clathrin to form budded vesicles. They also interact with accessory proteins that regulate coat assembly and disassembly, including dynamin for vesicle fission and uncoating factors after vesicle detachment.

Clinical relevance: Mutations in AP complex subunits can cause human disease. For instance, AP-4 deficiency syndrome is linked to neurodevelopmental disorders and spastic paraplegia, highlighting the importance of proper adaptor-mediated trafficking in neurons.

History: Adaptor proteins were identified in the 1990s as components of clathrin-coated vesicles, and the AP complex model has since become central to understanding intracellular trafficking.