Receptor coupling to different G-proteins and β-arrestins has been described for a number of GPCRs (G-protein-coupled receptors), suggesting a multi-state model of receptor activation in which each receptor can assume a number of different active conformations, each capable of promoting the coupling to a specific effector. Consistently, functional-selective ligands and biased agonists have been described to be able to induce and/or stabilize only a subset of specific active conformations. Furthermore, GPCR mutants deficient in selective coupling have been reported. Functional selective ligands and receptor mutants thus constitute unique tools to dissect the specific roles of different effectors, in particular among the Gi/o family. In the present mini-review, we focus on (i) the identification of functional selective OXT (oxytocin)-derived peptides capable of activating single Gi/o isoforms, namely Gi1 or Gi3; and (ii) the characterization of an SS (somatostatin) receptor SST5 mutant selectively impaired in its GoA coupling. These analogues and receptor mutants represent unique tools for examining the contribution of Gi/o isoforms in complex biological responses and open the way for the development of drugs with peculiar selectivity profiles.
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February 2013
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Conference Article|
January 29 2013
Deciphering the specific role of Gαi/o isoforms: functional selective oxytocin ligands and somatostatin SST5 receptor mutants
Marta Busnelli;
Marta Busnelli
*CNR, Institute of Neuroscience, Via Vanvitelli 32, 20129, Milan, Italy
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Erika Peverelli;
Erika Peverelli
†Endocrinology and Diabetology Unit, Department of Clinical Sciences and Community Health, University of Milan, Fondazione IRCCS Ca’Granda Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy
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Giovanna Mantovani;
Giovanna Mantovani
†Endocrinology and Diabetology Unit, Department of Clinical Sciences and Community Health, University of Milan, Fondazione IRCCS Ca’Granda Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy
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Anna Spada;
Anna Spada
†Endocrinology and Diabetology Unit, Department of Clinical Sciences and Community Health, University of Milan, Fondazione IRCCS Ca’Granda Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy
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Bice Chini
Bice Chini
1
*CNR, Institute of Neuroscience, Via Vanvitelli 32, 20129, Milan, Italy
1To whom correspondence should be addressed (emailb.chini@in.cnr.it).
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Biochem Soc Trans (2013) 41 (1): 166–171.
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Received:
October 31 2012
Citation
Marta Busnelli, Erika Peverelli, Giovanna Mantovani, Anna Spada, Bice Chini; Deciphering the specific role of Gαi/o isoforms: functional selective oxytocin ligands and somatostatin SST5 receptor mutants. Biochem Soc Trans 1 February 2013; 41 (1): 166–171. doi: https://doi.org/10.1042/BST20120306
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