Abstract
Adhesion G protein-coupled receptors (aGPCR) form the second largest class of GPCR. They are phylogenetically old and have been highly conserved during evolution. Mutations in representatives of this class are associated with severe diseases such as Usher Syndrome, a combined congenital deaf-blindness, or bifrontal parietal polymicrogyria. The main characteristics of aGPCR are their enormous size and the complexity of their N termini. They contain a highly conserved GPCR proteolytic site (GPS) and several functional domains that have been implicated in cell-cell and cell-matrix interactions. Adhesion GPCR have been proposed to serve a dual function as adhesion molecules and as classical receptors. However, until recently there was no proof that aGPCR indeed couple to G proteins or even function as classical receptors. In this review, we have summarized and discussed recent evidence that aGPCR present many functional features of classical GPCR, including multiple G protein-coupling abilities, G protein-independent signaling and oligomerization, but also specific signaling properties only found in aGPCR.
About the authors
Ines Liebscher studied medicine at the University of Leipzig. After completing her MD thesis at the Institute for Biochemistry at the Medical Faculty on the physiological relevance of an orphan GPCR she pursued a scientific career. The current focus of her research is the field of adhesion GPCR, which she studies in vitro and in vivo using transgenic mouse models. Ines Liebscher is currently leading a group in the Institute of Biochemistry at University of Leipzig.
Torsten Schöneberg studied medicine at the University of Greifswald, is professor of Molecular Biochemistry and leads the Institute for Biochemistry at the Medical Faculty of University of Leipzig, Germany. After completing his MD thesis at the Institute of Pharmacology at the Charité, Humboldt University of Berlin, he focused on GPCR and their signal transduction in the laboratories of J. Wess (NIDDK, NIH, Bethesda) and G. Schultz (Free University of Berlin) as a postdoc.
Simone Prömel studied biochemistry at the Free University of Berlin and is a junior group leader at the Institute for Biochemistry, Medical Faculty, University of Leipzig, Germany. Her group studies function and signaling mechanisms of adhesion GPCR in C. elegans and mouse models. Her interest in adhesion GPCR developed during her PhD in Dr. A. Russ’ laboratory at University of Oxford.
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