Adhesion G protein-coupled receptor

The human adhesion GPCR family. Members are defined by their unusual hybrid structure in which a large extracellular region often containing known protein modules is coupled to a seven span transmembrane region via a GPCR-Autoproteolsis INducing (GAIN) domain.

Adhesion G protein-coupled receptors (adhesion GPCRs) are a class of 33 human protein receptors with a broad distribution in embryonic and larval cells, cells of the reproductive tract, neurons, leukocytes, and a variety of tumours.[1] Adhesion GPCRs are found throughout metazoans and are also found in single-celled colony forming choanoflagellates such as Monosiga brevicollis and unicellular organisms such as Filasterea. The defining feature of adhesion GPCRs that distinguishes them from other GPCRs is their hybrid molecular structure. The extracellular region of adhesion GPCRs can be exceptionally long and contain a variety of structural domains that are known for the ability to facilitate cell and matrix interactions. Their extracellular region contains the membrane proximal GAIN (GPCR-Autoproteolsis INducing) domain. Crystallographic and experimental data has shown this structurally conserved domain to mediate autocatalytic processing at a GPCR-proteolytic site (GPS) proximal to the first transmembrane helix. Autocatalytic processing gives rise to an extracellular (α) and a membrane-spanning (β) subunit, which are associated non-covalently, resulting in expression of a heterodimeric receptor at the cell surface.[2][3] Ligand profiles and in vitro studies have indicated a role for adhesion GPCRs in cell adhesion and migration.[4] Work utilizing genetic models confined this concept by demonstrating that the primary function of adhesion GPCRs may relate to the proper positioning of cells in a variety of organ systems. Moreover, growing evidence implies a role of adhesion GPCRs in tumour cell metastasis.[5] Formal G protein-coupled signalling has been demonstrated for a number for adhesion GPCRs,[6][7] however, the orphan receptor status of many of the receptors still hampers full characterisation of potential signal transduction pathways. In 2011, the adhesion GPCR consortium was established to facilitate research of the physiological and pathological functions of adhesion GPCRs.

  1. ^ Hamann, J; Aust, G; Araç, D; Engel, FB; Formstone, C; Fredriksson, R; Hall, RA; Harty, BL; Kirchhoff, C; Knapp, B; Krishnan, A; Liebscher, I; Lin, HH; Martinelli, DC; Monk, KR; Peeters, MC; Piao, X; Prömel, S; Schöneberg, T; Schwartz, TW; Singer, K; Stacey, M; Ushkaryov, YA; Vallon, M; Wolfrum, U; Wright, MW; Xu, L; Langenhan, T; Schiöth, HB (April 2015). "International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G Protein-Coupled Receptors". Pharmacological Reviews. 67 (2): 338–67. doi:10.1124/pr.114.009647. PMC 4394687. PMID 25713288.
  2. ^ Araç, D; Boucard, AA; Bolliger, MF; Nguyen, J; Soltis, SM; Südhof, TC; Brunger, AT (Feb 14, 2012). "A novel evolutionarily conserved domain of cell-adhesion GPCRs mediates autoproteolysis". The EMBO Journal. 31 (6): 1364–78. doi:10.1038/emboj.2012.26. PMC 3321182. PMID 22333914.
  3. ^ Lin, HH; Chang, GW; Davies, JQ; Stacey, M; Harris, J; Gordon, S (Jul 23, 2004). "Autocatalytic cleavage of the EMR2 receptor occurs at a conserved G protein-coupled receptor proteolytic site motif". The Journal of Biological Chemistry. 279 (30): 31823–32. doi:10.1074/jbc.M402974200. PMID 15150276.
  4. ^ Langenhan, T; Aust, G; Hamann, J (May 21, 2013). "Sticky Signaling - Adhesion Class G Protein-Coupled Receptors Take the Stage". Science Signaling. 6 (276): r3. doi:10.1126/scisignal.2003825. PMID 23695165. S2CID 6958640.
  5. ^ Yang, L; Xu, L (April 2012). "GPR56 in cancer progression: current status and future perspective". Future Oncology (London, England). 8 (4): 431–40. doi:10.2217/fon.12.27. PMID 22515446.
  6. ^ Steinert, M; Wobus, M; Boltze, C; Schütz, A; Wahlbuhl, M; Hamann, J; Aust, G (November 2002). "Expression and regulation of CD97 in colorectal carcinoma cell lines and tumour tissues". The American Journal of Pathology. 161 (5): 1657–67. doi:10.1016/S0002-9440(10)64443-4. PMC 1850798. PMID 12414513.
  7. ^ Aust G (2010). "Adhesion-GPCRs in Tumorigenesis". In Yona S, Stacey M (eds.). Adhesion-GPCRs: Structure to Function. Advances in Experimental Medicine and Biology. Vol. 706. Landes Bioscience and Springer Science+Business Media, LLC. pp. 109–20. doi:10.1007/978-1-4419-7913-1_9. ISBN 978-1-4419-7912-4. PMC 5389670. PMID 21618830.