Introduction: History of the Adhesion GPCR Field

  • Jörg HamannEmail author
  • Alexander G. PetrenkoEmail author
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 234)

Graphical Abstract

Development of the aGPCR scientific field based on PubMed-listed research articles and selected key findings


Since the discovery of adhesion G-protein-coupled receptors (aGPCRs) 20 years ago, reverse genetics approaches have dominated the elucidation of their function and work mechanisms. Seminal findings in this field comprise the description of aGPCRs as seven-transmembrane (7TM) molecules with an extended extracellular region, the identification of matricellular ligands that bind to distinct protein folds at the N-terminus, the clarification of an autoproteolytic cleavage event at a juxtamembranous GPCR proteolysis site (GPS), the elucidation of the crystal structure of the GPCR autoproteolysis-inducing (GAIN) domain that embeds the GPS and connects the receptor fragments, the demonstration that a short N-terminal sequence of the seven-transmembrane (7TM) region can serve as a tethered agonist, and, recently, the notification that aGPCRs can serve as mechanosensors. We here discuss how these discoveries have moved forward aGPCR research and, finally, linked the field to the GPCR field. We argue that crucial questions remain to be addressed before we can fully appreciate the biological nature of these fascinating receptors.


Adhesion GPCRs History Biology Structure Signaling Pharmacology 



The writing of this manuscript was supported by the Deutsche Forschungsgemeinschaft (Research Unit 2149) and by grants of the Thyssen Foundation (2015-00387) to JH and the Russian Science Foundation (14-14-01195) to AGP.

Competing Financial Interests The authors declare no competing financial interests.


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Copyright information

© Springer International Publishing AG 2016

Authors and Affiliations

  1. 1.Department of Experimental ImmunologyK0-144, Academic Medical Center, University of AmsterdamAmsterdamThe Netherlands
  2. 2.Laboratory of Receptor Cell BiologyShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of SciencesMoscowRussia

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