Adhesion G protein-coupled receptors-Candidate metabotropic mechanosensors and novel drug targets

Basic Clin Pharmacol Toxicol. 2020 Jun:126 Suppl 6:5-16. doi: 10.1111/bcpt.13223. Epub 2019 Apr 4.

Abstract

While a wide range of G protein-coupled receptors (GPCR) have emerged as prime targets for pharmacological intervention long ago, a distinct group of GPCR has only recently been identified and become a research subject to fundamental and clinical scientists. Adhesion-type GPCR (aGPCR) are exceptional members of the GPCR superfamily in many aspects: structurally, they appear as chimeric surface molecules that possess signature domains of heptahelical (7TM) and adhesion proteins, many aGPCR are autoproteolytically processed, and several homologues have lately been shown to operate as mechanosensors. Bound together by the recent discovery of tethered agonism in aGPCR, these molecular and functional features have entered first models on how aGPCR are activated. Here, I briefly review recent discoveries pertaining to the role of aGPCR as metabotropic mechanosensors that control a large variety of processes in all major tissue types.

Keywords: G protein-coupled receptors; adhesion GPCR; autoproteolysis; cancer; monobodies.

Publication types

  • Review

MeSH terms

  • Cell Adhesion Molecules / metabolism
  • Cell Membrane / metabolism
  • Drug Development
  • Humans
  • Mechanotransduction, Cellular
  • Platelet Glycoprotein GPIb-IX Complex / chemistry*
  • Protein Binding
  • Receptors, G-Protein-Coupled / chemistry*
  • Receptors, G-Protein-Coupled / metabolism*
  • Signal Transduction
  • Structure-Activity Relationship

Substances

  • Cell Adhesion Molecules
  • Platelet Glycoprotein GPIb-IX Complex
  • Receptors, G-Protein-Coupled
  • adhesion receptor