This article is part of the Research Topic Neuropeptide GPCRs in neuroendocrinology


Front. Endocrinol., 16 November 2012 |

The VPAC1 receptor: structure and function of a class B GPCR prototype

A. Couvineau*, E. Ceraudo, Y.-V. Tan, P. Nicole and M. Laburthe*
  • Faculté de Médecine Xavier Bichat, INSERM 773/Centre de Recherche Biomédicale Bichat Beaujon (CRB3), Université Paris 7, Paris Cedex 18, France

The class B G protein-coupled receptors (GPCRs) represents a small sub-family encompassing 15 members, and are very promising targets for the development of drugs to treat many diseases such as chronic inflammation, neurodegeneration, diabetes, stress, and osteoporosis. The VPAC1 receptor which is an archetype of the class B GPCRs binds Vasoactive Intestinal Peptide (VIP), a neuropeptide widely distributed in central and peripheral nervous system modulating many physiological processes including regulation of exocrine secretions, hormone release, foetal development, immune response … VIP appears to exert beneficial effect in neurodegenerative and inflammatory diseases. This article reviews the current knowledge regarding the structure and molecular pharmacology of VPAC1 receptors. Over the past decade, structure–function relationship studies have demonstrated that the N-terminal ectodomain (N-ted) of VPAC1 plays a pivotal role in VIP recognition. The use of different approaches such as directed mutagenesis, photoaffinity labeling, Nuclear Magnetic Resonance (NMR), molecular modeling, and molecular dynamic simulation has led to demonstrate that: (1) the central and C-terminal part of the VIP molecule interacts with the N-ted of VPAC1 receptor which is itself structured as a « Sushi » domain; (2) the N-terminal end of the VIP molecule interacts with the first transmembrane domain of the receptor where three residues (K143, T144, and T147) play an important role in VPAC1 interaction with the first histidine residue of VIP.

Keywords: GPCR, photolabeling, VPAC1, VIP, mutagenesis, inflammation, neuroprotection, molecular modeling

Citation: Couvineau A, Ceraudo E, Tan Y-V, Nicole P and Laburthe M (2012) The VPAC1 receptor: structure and function of a class B GPCR prototype. Front. Endocrin. 3:139. doi: 10.3389/fendo.2012.00139

Received: 31 August 2012; Paper pending published: 26 September 2012;
Accepted: 26 October 2012; Published online: 16 November 2012.

Edited by:

Hubert Vaudry, University of Rouen, France

Reviewed by:

James Waschek, University of California at Los Angeles, USA
Daniel Fourmy, University of Toulouse 3, France

Copyright © 2012 Couvineau, Ceraudo, Tan, Nicole and Laburthe. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.

*Correspondence: A. Couvineau and M. Laburthe, Faculté de Médecine X. Bichat, INSERM U773/CRB3, 16 Rue Henri Huchard, 75018 Paris, France. e-mail:;