Proteins synthesized on the ribosome and processed in the endoplasmic reticulum are transported from the Golgi apparatus to the trans-Golgi network (TGN), and from there via small carrier vesicles to their final destination compartment. These vesicles have specific coat proteins (such as clathrin or coatomer) that are important for cargo selection and direction of transport [1]. Clathrin coats contain both clathrin (acts as a scaffold) and adaptor complexes that link clathrin to receptors in coated vesicles. Clathrin-associated protein complexes are believed to interact with the cytoplasmic tails of membrane proteins, leading to their selection and concentration. The two major types of clathrin adaptor complexes are the heterotetrameric adaptor protein (AP) complexes, and the monomeric GGA (Golgi-localising, Gamma-adaptin ear domain homology, ARF-binding proteins) adaptors [2, 3].

AP (adaptor protein) complexes are found in coated vesicles and clathrin-coated pits. AP complexes connect cargo proteins and lipids to clathrin at vesicle budding sites, as well as binding accessory proteins that regulate coat assembly and disassembly (such as AP180, epsins and auxilin). There are different AP complexes in mammals. AP1 is responsible for the transport of lysosomal hydrolases between the TGN and endosomes [4]. AP2 associates with the plasma membrane and is responsible for endocytosis [5]. AP3 is responsible for protein trafficking to lysosomes and other related organelles [6]. AP4 is less well characterised. AP complexes are heterotetramers composed of two large subunits (adaptins), a medium subunit (mu) and a small subunit (sigma). For example, in AP1 these subunits are gamma-1-adaptin, beta-1-adaptin, mu-1 and sigma-1, while in AP2 they are alpha-adaptin, beta-2-adaptin, mu-2 and sigma-2. Each subunit has a specific function. Adaptins recognise and bind to clathrin through their hinge region (clathrin box), and recruit accessory proteins that modulate AP function through their C-terminal ear (appendage) domains. Mu recognises tyrosine-based sorting signals within the cytoplasmic domains of transmembrane cargo proteins [7]. One function of clathrin and AP2 complex-mediated endocytosis is to regulate the number of GABA(A) receptors available at the cell surface [8].

This entry represents the mu subunit of various clathrin adaptors (AP1, AP2 and AP3) [9]. The mu subunit regulates the coupling of clathrin lattices with particular membrane proteins by self-phosphorylation via a mechanism that is still unclear [10]. The mu subunit possesses a highly conserved N-terminal domain of around 230 amino acids, which may be the region of interaction with other AP proteins; a linker region of between 10 and 42 amino acids; and a less well-conserved C-terminal domain of around 190 amino acids, which may be the site of specific interaction with the protein being transported in the vesicle [11].

1. COP and clathrin-coated vesicle budding: different pathways, common approaches. Curr. Opin. Cell Biol. 16, 379-91
2. Do different endocytic pathways make different synaptic vesicles? Curr. Opin. Neurobiol. 17, 374-80
3. Adaptins: the final recount. Mol. Biol. Cell 12, 2907-20
4. Adaptor protein complex 1 mediates the transport of lysosomal proteins from a Golgi-like organelle to peripheral vacuoles in the primitive eukaryote Giardia lamblia. Mol. Biol. Cell 15, 3053-60
5. Differential requirements for AP-2 in clathrin-mediated endocytosis. J. Cell Biol. 162, 773-9
6. Re-routing of the invariant chain to the direct sorting pathway by introduction of an AP3-binding motif from LIMP II. Eur. J. Cell Biol. 85, 457-67
7. Dual interaction of synaptotagmin with mu2- and alpha-adaptin facilitates clathrin-coated pit nucleation. EMBO J. 19, 6011-9
8. Phospholipase C-related inactive protein is implicated in the constitutive internalization of GABAA receptors mediated by clathrin and AP2 adaptor complex. J. Neurochem. 101, 898-905
9. Study of the interaction of the medium chain mu 2 subunit of the clathrin-associated adapter protein complex 2 with cytotoxic T-lymphocyte antigen 4 and CD28. Biochem. J. 359, 427-34
10. The medium chains of the mammalian clathrin-associated proteins have a homolog in yeast. Eur. J. Biochem. 202, 569-74

Proteins synthesized on the ribosome and processed in the endoplasmic reticulum are transported f
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