Oligomerization of GPCRs involved in endocrine regulation
- G Kleinau, Institute of Experimental Pediatric Endocrinology, Charité-Universitätsmedizin Berlin, Berlin, 13353, Germany
- A Müller, Institute of Experimental Pediatric Endocrinology, Charité-Universitätsmedizin Berlin, Berlin, Germany
- H Biebermann, Institute of Experimental Pediatric Endocrinology, Charite Campus Virchow, Berlin, Germany
- Correspondence: Heike Biebermann, Email: heike.biebermann{at}charite.de
Abstract
More than 800 different human membrane-spanning G-protein coupled receptors (GPCRs) serve as signal transducers at biological barriers. These receptors are activated by a wide variety of ligands such as peptides, ions, and hormones, and are able to activate a diverse set of intracellular signaling pathways. GPCRs are of central importance in endocrine regulation, which underpins the significance of comprehensively studying these receptors and interrelated systems. During the last decades, the capacity for multimerization of GPCRs was found to be a common and functionally relevant property. The interaction between GPCR monomers results in higher order complexes such as homomers (identical receptor subtype) or heteromers (different receptor subtypes), which may be present in a specific and dynamic monomer/oligomer equilibrium. It is widely accepted that the oligomerization of GPCRs is a mechanism for determining the fine-tuning and expansion of cellular processes by modification of ligand action, expression levels, and related signaling outcome. Accordingly, oligomerization provides exciting opportunities to optimize pharmacological treatment with respect to receptor target and tissue selectivity or for the development of diagnostic tools. On the other hand, GPCR heteromerization may be a potential reason for the undesired side effects of pharmacological interventions, faced with numerous and common mutual signaling modifications in heteromeric constellations. Finally, detailed deciphering of the physiological occurrence and relevance of specific GPCR/GPCR-ligand interactions poses a future challenge. This review will tackle aspects of GPCR oligomerization with specific emphasis on family A GPCRs involved in endocrine regulation, whereby only a subset of these receptors will be discussed in detail.
- Received 5 March 2016
- Revision received 25 April 2016
- Accepted 4 May 2016
- Accepted Preprint first posted online on 5 May 2016