DefinitionThis section has been translated automatically.
Adaptor protein complexes (AP complexes) are ubiquitously expressed protein complexes found in all mammals. Adapter proteins are essential for the formation of clathrin-coated vesicles and, along with clathrin , are the most abundant proteins in clathrin vesicles.
Adapter proteins mediate the binding of clathrin to membranes. Furthermore, they can interact with a variety of accessory and regulatory proteins through various other binding domains.
All adaptors have a very characteristic structure that resembles a head with long ears under the electron microscope. The individual subunits are called adaptins. With their many binding and interaction sites, these protein complexes are organizational centers of clathrin-mediated endocytosis: they connect the scaffold molecule clathrin to membranes, bind certain cargo molecules, and recruit a swarm of helper molecules to the sites of vesicle formation
General informationThis section has been translated automatically.
So far, four heterotetramers (each consisting of four different polypeptides) adaptor protein complexes have been identified.
- These complexes, AP-1 to AP-4, bind to the heavy chains of clathrin, to membrane lipids and membrane proteins and thus mediate the binding of clathrin to membranes.
- AP-1 mediates the formation of "clathrin-coated vesicles" (CCV) on the trans-Golgi network (TGN), the last compartment of the protein synthesis apparatus in the secretory transport pathway.
- AP-2 mediates the formation of clathrin-coated vesicles at the plasma membrane. AP2 Is exclusively located at the plasma membrane and mediates the internalization of membrane proteins there.
- For AP-3 a direct clathrin binding is proven. For AP1 and AP4 similar transport and sorting functions at the TGN and/or the endosomes could be shown.
- As the only representative of the heterotetrameric adaptor complexes, AP4 does not have a typical clathrin box sequence, which is why the involvement of AP4 in the formation of CCVs is controversial.
The second large subunit of the adaptor complexes has the lowest degree of homology (~25%) and for historical reasons is designated in the order of discovery as gamma for AP-1, alpha for AP-2, delta for AP-3 and epsilon for AP-4. The two smaller proteins, middle subunits are designated u and sigma.
In addition to the 4 ubiquitously expressed adaptor complexes, there are two further tissue-specific expressed variants: AP1B in epithelial cells and AP3B in neuronal cells. In addition, several isoforms and splice variants of adaptor subunits have been identified whose function is largely unknown at present.
The absence of individual subunits of APs has far-reaching consequences depending on the organism. The knock-out of individual subunits of AP1, AP2 or AP4 in the mouse is lethal
Note(s)This section has been translated automatically.
A dysfunction of AP complexes is associated with a variety of hereditary diseases, including:
- MEDNIK syndrome (mental retardation, enteropathy, deafness, peripheral neuropathy, ichthyosis and keratoderma)
- Fried syndrome (delayed psychomotor development, hydrocephalus and facial dysmorphia)
- HPS syndrome(Hermansky-Pudlak syndrome)
- HSP paraplegia (hereditary spastic paraplegia).
LiteratureThis section has been translated automatically.
- Bretscher A et al (2000) ERM-Merlin and EBP50 protein families in plasma membrane organization and function. Annu Rev Cell Dev Biol 16: 113-143.
- Bretscher A et al (2002) ERM proteins and merlin: integrators at the cell cortex. Nat Rev Mol Cell Biol 3: 586-99.
- Tsukita S et al (1997) ERM proteins: head-to-tail regulation of actinplasma membrane interaction. Trends Biochem Sci 22: 53-58.