New functions and signaling mechanisms for the class of adhesion G protein-coupled receptors

Ines Liebscher, Brian Ackley, Demet Araç, Donna M. Ariestanti, Gabriela Aust, Byoung il Bae, Bigyan R. Bista, James P. Bridges, Joseph G. Duman, Felix B. Engel, Stefanie Giera, André M. Goffinet, Randy A. Hall, Jörg Hamann, Nicole Hartmann, Hsi Hsien Lin, Mingyao Liu, Rong Luo, Amit Mogha, Kelly R. MonkMiriam C. Peeters, Simone Prömel, Susanne Ressl, Helgi B. Schiöth, Séverine M. Sigoillot, Helen Song, William S. Talbot, Gregory G. Tall, James P. White, Uwe Wolfrum, Lei Xu, Xianhua Piao

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

The class of adhesion G protein-coupled receptors (aGPCRs), with 33 human homologs, is the second largest family of GPCRs. In addition to a seven-transmembrane α-helix-a structural feature of all GPCRs-the class of aGPCRs is characterized by the presence of a large N-terminal extracellular region. In addition, all aGPCRs but one (GPR123) contain a GPCR autoproteolysis-inducing (GAIN) domain that mediates autoproteolytic cleavage at the GPCR autoproteolysis site motif to generate N- and a C-terminal fragments (NTF and CTF, respectively) during protein maturation. Subsequently, the NTF and CTF are associated noncovalently as a heterodimer at the plasma membrane. While the biological function of the GAIN domain-mediated autocleavage is not fully understood, mounting evidence suggests that the NTF and CTF possess distinct biological activities in addition to their function as a receptor unit. We discuss recent advances in understanding the biological functions, signaling mechanisms, and disease associations of the aGPCRs.

Original languageEnglish (US)
Pages (from-to)43-64
Number of pages22
JournalAnnals of the New York Academy of Sciences
Volume1333
Issue number1
DOIs
StatePublished - Dec 1 2014

Keywords

  • Adhesion G protein-coupled receptor
  • Cancer
  • Development
  • Myelination
  • Signal transduction
  • Structural biology
  • Synaptogenesis

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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  • Cite this

    Liebscher, I., Ackley, B., Araç, D., Ariestanti, D. M., Aust, G., Bae, B. I., Bista, B. R., Bridges, J. P., Duman, J. G., Engel, F. B., Giera, S., Goffinet, A. M., Hall, R. A., Hamann, J., Hartmann, N., Lin, H. H., Liu, M., Luo, R., Mogha, A., ... Piao, X. (2014). New functions and signaling mechanisms for the class of adhesion G protein-coupled receptors. Annals of the New York Academy of Sciences, 1333(1), 43-64. https://doi.org/10.1111/nyas.12580