Clathrin adaptor protein

Last updated
Clathrin adaptor complex small chain
Identifiers
SymbolClat_adaptor_s
Pfam PF01217
InterPro IPR022775

Clathrin adaptor proteins, also known as adaptins, are vesicular transport adaptor proteins associated with clathrin. These proteins are synthesized in the ribosomes, processed in the endoplasmic reticulum and transported from the Golgi apparatus to the trans-Golgi network, and from there via small carrier vesicles to their final destination compartment. The association between adaptins and clathrin are important for vesicular cargo selection and transporting. [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. Therefore, adaptor proteins are responsible for the recruitment of cargo molecules into a growing clathrin-coated pits. [2] The two major types of clathrin adaptor complexes are the heterotetrameric vesicular transport adaptor proteins (AP1-5), and the monomeric GGA (Golgi-localising, Gamma-adaptin ear homology, ARF-binding proteins) adaptors. [3] [4] Adaptins are distantly related to the other main type of vesicular transport proteins, the coatomer subunits, sharing between 16% and 26% of their amino acid sequence. [5]

Contents

Adaptor protein (AP) 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 trans-Golgi network, and endosomes. [6] AP2 adaptor complex associates with the plasma membrane and is responsible for endocytosis. [7] AP3 is responsible for protein trafficking to lysosomes and other related organelles. [8] 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. [9] One function of clathrin and AP2 complex-mediated endocytosis is to regulate the number of GABAA receptors available at the cell surface . [10]

See also

Related Research Articles

Clathrin Protein playing a major role in the formation of coated vesicles

Clathrin is a protein that plays a major role in the formation of coated vesicles. Clathrin was first isolated and named by Barbara Pearse in 1976. It forms a triskelion shape composed of three clathrin heavy chains and three light chains. When the triskelia interact they form a polyhedral lattice that surrounds the vesicle, hence the protein's name, which is derived from the Latin clathrum meaning lattice. Coat-proteins, like clathrin, are used to build small vesicles in order to transport molecules within cells. The endocytosis and exocytosis of vesicles allows cells to communicate, to transfer nutrients, to import signaling receptors, to mediate an immune response after sampling the extracellular world, and to clean up the cell debris left by tissue inflammation. The endocytic pathway can be hijacked by viruses and other pathogens in order to gain entry to the cell during infection.

COPI Protein complex coating vesicles transporting proteins from the Golgi complex to the rough endoplasmic reticulum

COPI is a coatomer, a protein complex that coats vesicles transporting proteins from the cis end of the Golgi complex back to the rough endoplasmic reticulum (ER), where they were originally synthesized, and between Golgi compartments. This type of transport is retrograde transport, in contrast to the anterograde transport associated with the COPII protein. The name "COPI" refers to the specific coat protein complex that initiates the budding process on the cis-Golgi membrane. The coat consists of large protein subcomplexes that are made of seven different protein subunits, namely α, β, β', γ, δ, ε and ζ.

Vesicular transport adaptor protein

Vesicular transport adaptor proteins are proteins involved in forming complexes that function in the trafficking of molecules from one subcellular location to another. These complexes concentrate the correct cargo molecules in vesicles that bud or extrude off of one organelle and travel to another location, where the cargo is delivered. While some of the details of how these adaptor proteins achieve their trafficking specificity has been worked out, there is still much to be learned.

The coatomer is a protein complex that coats membrane-bound transport vesicles. Two types of coatomers are known:

AP2 adaptor complex

The AP2 adaptor complex is a multimeric protein that works on the cell membrane to internalize cargo in clathrin-mediated endocytosis. It is a stable complex of four adaptins which give rise to a structure that has a core domain and two appendage domains attached to the core domain by polypeptide linkers. These appendage domains are sometimes called 'ears'. The core domain binds to the membrane and to cargo destined for internalisation. The alpha and beta appendage domains bind to accessory proteins and to clathrin. Their interactions allow the temporal and spatial regulation of the assembly of clathrin-coated vesicles and their endocytosis.

AP2M1

AP-2 complex subunit mu is a protein that in humans is encoded by the AP2M1 gene.

Adaptor-related protein complex 2, alpha 1

AP-2 complex subunit alpha-1 is a protein that in humans is encoded by the AP2A1 gene.

AP1M1

AP-1 complex subunit mu-1 is a protein that in humans is encoded by the AP1M1 gene.

AP1G1

AP-1 complex subunit gamma-1 is a protein that in humans is encoded by the AP1G1 gene.

AP1B1

AP-1 complex subunit beta-1 is a protein that in humans is encoded by the AP1B1 gene.

AP2B1 Protein-coding gene in the species Homo sapiens

AP-2 complex subunit beta is a protein that in humans is encoded by the AP2B1 gene.

AP1S1

AP-1 complex subunit sigma-1A is a protein that in humans is encoded by the AP1S1 gene.

AP1G2

AP-1 complex subunit gamma-like 2 is a protein that in humans is encoded by the AP1G2 gene.

AP3M1

AP-3 complex subunit mu-1 is a protein that in humans is encoded by the AP3M1 gene.

Synergin gamma

Synergin gamma also known as AP1 subunit gamma-binding protein 1 (AP1GBP1) is a protein that in humans is encoded by the SYNRG gene.

AP2S1

AP-2 complex subunit sigma is a protein that in humans is encoded by the AP2S1 gene.

AP4M1

AP-4 complex subunit mu-1 is a protein that in humans is encoded by the AP4M1 gene.

Beta2-adaptin C-terminal domain

The C-terminal domain ofBeta2-adaptin is a protein domain is involved in cell trafficking by aiding import and export of substances in and out of the cell.

Exomer is a heterotetrameric protein complex similar to COPI and other adaptins. It was first described in the yeast Saccharomyces cerevisiae. Exomer is a cargo adaptor important in transporting molecules from the Golgi apparatus toward the cell membrane. The vesicles it is found on are different from COPI vesicles in that they do not appear to have a "coat" or "scaffold" around them.

References

  1. ↑ McMahon HT, Mills IG (August 2004). "COP and clathrin-coated vesicle budding: different pathways, common approaches". Curr. Opin. Cell Biol. 16 (4): 379–91. doi:10.1016/j.ceb.2004.06.009. PMID   15261670.
  2. ↑ Weigel, Aubrey V.; Tamkun, Michael M.; Krapf, Diego (2013-11-26). "Quantifying the dynamic interactions between a clathrin-coated pit and cargo molecules". Proceedings of the National Academy of Sciences. 110 (48): E4591–E4600. Bibcode:2013PNAS..110E4591W. doi:10.1073/pnas.1315202110. PMC   3845133 . PMID   24218552.
  3. ↑ Voglmaier SM, Edwards RH (June 2007). "Do different endocytic pathways make different synaptic vesicles?". Curr. Opin. Neurobiol. 17 (3): 374–80. doi:10.1016/j.conb.2007.04.002. PMID   17449236. S2CID   44740900.
  4. ↑ Boehm M, Bonifacino JS (October 2001). "Adaptins: the final recount". Mol. Biol. Cell. 12 (10): 2907–20. doi:10.1091/mbc.12.10.2907. PMC   60144 . PMID   11598180.
  5. ↑ Boehm, Markus; Bonifacino, Juan S. (October 2001). "Adaptins". Molecular Biology of the Cell. 12 (10): 2907–2920. doi:10.1091/mbc.12.10.2907. ISSN   1059-1524. PMC   60144 . PMID   11598180.
  6. ↑ Touz MC, Kulakova L, Nash TE (July 2004). "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 (7): 3053–60. doi:10.1091/mbc.E03-10-0744. PMC   452563 . PMID   15107467.
  7. ↑ Conner SD, Schmid SL (September 2003). "Differential requirements for AP-2 in clathrin-mediated endocytosis". J. Cell Biol. 162 (5): 773–9. doi:10.1083/jcb.200304069. PMC   2172816 . PMID   12952931.
  8. ↑ Gupta SN, Kloster MM, Rodionov DG, Bakke O (June 2006). "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 (6): 457–67. doi:10.1016/j.ejcb.2006.02.001. PMID   16542748.
  9. ↑ Haucke V, Wenk MR, Chapman ER, Farsad K, De Camilli P (November 2000). "Dual interaction of synaptotagmin with mu2- and alpha-adaptin facilitates clathrin-coated pit nucleation". EMBO J. 19 (22): 6011–9. doi:10.1093/emboj/19.22.6011. PMC   305843 . PMID   11080148.
  10. ↑ Kanematsu T, Fujii M, Mizokami A, Kittler JT, Nabekura J, Moss SJ, Hirata M (May 2007). "Phospholipase C-related inactive protein is implicated in the constitutive internalization of GABAA receptors mediated by clathrin and AP2 adaptor complex". J. Neurochem. 101 (4): 898–905. doi: 10.1111/j.1471-4159.2006.04399.x . PMID   17254016. S2CID   22361369.
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