Co-receptor
The term co-receptor is prominent in literature regarding signal transduction, the process by which external stimuli regulate internal cellular functioning.
[1] The key to optimal cellular functioning is maintained by possessing specific machinery that can carry out tasks efficiently and effectively.
Specifically, the process through which intermolecular reactions forward and amplify extracellular signals across the cell surface has developed to occur by two mechanisms.
[2] The CD family of co-receptors are a well-studied group of extracellular receptors found in immunological cells.
Boehme et al. demonstrated this interesting dual outcome by blocking the binding of CD4 to MHC-II which prevented the programmed cell death reaction that active T-cells typically display.
The CD4 receptor in particular interacts with murine MHC-II following the "ball-on-stick" model, where the Phe-43 ball fits into the conserved hydrophobic α2 and β2 domain residues.
[7] Perhaps the most famous and well-studied of the CCR family is CCR5 (and its near-homologue CXCR4) which acts as the primary co-receptor for HIV viral infection.
Due to the commonality of structures found throughout the family, CCR2b, CCR3, and CCR8 can be utilized by some HIV strains as co-receptors to facilitate infection.
[7][8] CCR5's affinity for MIP makes it of great interest for practical applications such as tissue engineering, where attempts are being made to control host inflammatory and immunological responses at a cellular signalling level.
LRP5 (low-density lipoprotein receptor-related protein 5) acts as a co-receptor for the Wnt-family of glycoproteins which regulate bone mass.
[10] The neuropilin co-receptor family mediates binding of VEGF in conjunction with the VEGFR1/VEGFR2 and Plexin signaling receptors, and therefore also plays a role in tumor vascular development.
Upon binding TGF-β, the receptor is internalized via endocytosis through CD109's action which lowers signal transmission into the cell.
[11] In this case, the co-receptor is functioning in a critical regulatory manner to reduce signals that instruct the cell to grow and migrate – the hallmarks of cancer.
[2] In order to infect a cell, the envelope glycoprotein GP120 of the HIV virus interacts with CD4 (acting as the primary receptor) and a co-receptor: either CCR5 or CXCR4.
[12] In approximately half of all HIV cases, the viruses using the CCR5 co-receptor seem to favor immediate infection and transmission while those using the CXCR4 receptor do not present until later in the immunologically suppressed stage of the disease.
[13] Recent evidence suggests that some forms of HIV also use the large integrin a4b7 receptor to facilitate increased binding efficiency in mucosal tissues.
[14] It is possible to perform a CD4 co-receptor blockade, using antibodies, in order to lower T cell activation and counteract autoimmune disorders.
[15] This blockade appears to elicit a "dominant" effect, that is to say, once blocked, the T cells do not regain their ability to become active.
[20] Although the exact mechanism is still unknown, CD8 co-receptors have been shown to enhance T-cell activation and TGF-β-mediated immune suppression.
[22] Sortilin, the p75 co-receptor, has been found in natural killer cells, but with only low levels of neurotrophin receptor.
