For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
29
views
113
references
 Top references
cited by
12
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      338
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Biological Significance of GPCR Heteromerization in the Neuro-Endocrine System

      review-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Clustering of proteins in higher order complexes is a common theme in biology and profoundly influences protein function. The idea that seven-transmembrane spanning G protein-coupled receptors (GPCRs) might form dimers or higher order oligomeric complexes has been formulated more than 20 years ago. Since then, this phenomenon has been investigated with many different biochemical and biophysical techniques. The more recent notion of GPCR heteromerization describes the specific association of two different GPCRs. GPCR heteromerization may be of primary importance in neuroendocrinology, as this may explain at least some of the functional crosstalks described between different hormonal systems. Importantly, many GPCR heteromers have distinct functional properties compared to their corresponding homomers. Heteromer-specific pharmacological profiles might be exploited for drug design and open new therapeutic options. GPCR heteromerization has been first studied in heterologous expression systems. Today, increasing evidence for the existence of GPCR heteromers in endogenous systems is emerging providing crucial evidence for the physiological function of GPCR heteromerization.

          Related collections

          Most cited references113

          • Record: found
          • Abstract: found
          • Article: not found

          Structures of the CXCR4 chemokine GPCR with small-molecule and cyclic peptide antagonists.

          Beili Wu, Ellen Chien, Clifford D Mol … (2010)
          Chemokine receptors are critical regulators of cell migration in the context of immune surveillance, inflammation, and development. The G protein-coupled chemokine receptor CXCR4 is specifically implicated in cancer metastasis and HIV-1 infection. Here we report five independent crystal structures of CXCR4 bound to an antagonist small molecule IT1t and a cyclic peptide CVX15 at 2.5 to 3.2 angstrom resolution. All structures reveal a consistent homodimer with an interface including helices V and VI that may be involved in regulating signaling. The location and shape of the ligand-binding sites differ from other G protein-coupled receptors and are closer to the extracellular surface. These structures provide new clues about the interactions between CXCR4 and its natural ligand CXCL12, and with the HIV-1 glycoprotein gp120.
          Article 0 comments Cited 448 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            An amino-acid taste receptor.

            Greg Nelson, Jayaram Chandrashekar, Mark A Hoon … (2002)
            The sense of taste provides animals with valuable information about the nature and quality of food. Mammals can recognize and respond to a diverse repertoire of chemical entities, including sugars, salts, acids and a wide range of toxic substances. Several amino acids taste sweet or delicious (umami) to humans, and are attractive to rodents and other animals. This is noteworthy because L-amino acids function as the building blocks of proteins, as biosynthetic precursors of many biologically relevant small molecules, and as metabolic fuel. Thus, having a taste pathway dedicated to their detection probably had significant evolutionary implications. Here we identify and characterize a mammalian amino-acid taste receptor. This receptor, T1R1+3, is a heteromer of the taste-specific T1R1 and T1R3 G-protein-coupled receptors. We demonstrate that T1R1 and T1R3 combine to function as a broadly tuned L-amino-acid sensor responding to most of the 20 standard amino acids, but not to their D-enantiomers or other compounds. We also show that sequence differences in T1R receptors within and between species (human and mouse) can significantly influence the selectivity and specificity of taste responses.
            Article 0 comments Cited 297 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Identification of a serotonin/glutamate receptor complex implicated in psychosis.

              Javier Gonzalez-Maeso, Rosalind Ang, Tony Yuen … (2008)
              The psychosis associated with schizophrenia is characterized by alterations in sensory processing and perception. Some antipsychotic drugs were identified by their high affinity for serotonin 5-HT2A receptors (2AR). Drugs that interact with metabotropic glutamate receptors (mGluR) also have potential for the treatment of schizophrenia. The effects of hallucinogenic drugs, such as psilocybin and lysergic acid diethylamide, require the 2AR and resemble some of the core symptoms of schizophrenia. Here we show that the mGluR2 interacts through specific transmembrane helix domains with the 2AR, a member of an unrelated G-protein-coupled receptor family, to form functional complexes in brain cortex. The 2AR-mGluR2 complex triggers unique cellular responses when targeted by hallucinogenic drugs, and activation of mGluR2 abolishes hallucinogen-specific signalling and behavioural responses. In post-mortem human brain from untreated schizophrenic subjects, the 2AR is upregulated and the mGluR2 is downregulated, a pattern that could predispose to psychosis. These regulatory changes indicate that the 2AR-mGluR2 complex may be involved in the altered cortical processes of schizophrenia, and this complex is therefore a promising new target for the treatment of psychosis.
              Article 0 comments Cited 192 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): Front Endocrinol (Lausanne)
                Journal ID (iso-abbrev): Front Endocrinol (Lausanne)
                Journal ID (publisher-id): Front. Endocrin.
                Title: Frontiers in Endocrinology
                Publisher: Frontiers Research Foundation
                ISSN (Electronic): 1664-2392
                Publication date (Electronic preprint): 19 December 2010
                Publication date (Electronic): 01 February 2011
                Publication date Collection: 2011
                Volume: 2
                Electronic Location Identifier: 2
                Affiliations
                [1] 1simpleDepartment of Endocrinology, Metabolism and Cancer, INSERM U1016, Institut Cochin Paris, France
                [2] 2simpleCNRS UMR 8104 Paris, France
                [3] 3simpleUniversity Paris Descartes Paris, France
                Author notes

                Edited by: Regina Pekelmann Markus, University of São Paulo, Brazil

                Reviewed by: Regina Pekelmann Markus, University of São Paulo, Brazil; Krystyna Skwarlo-Sonta, University of Warsaw, Poland; Sandra Helena Poliselli Farsky, University of São Paulo, Brazil

                *Correspondence: Ralf Jockers, Institut Cochin, 22 rue Méchain, 75014 Paris, France. e-mail: ralf.jockers@ 123456inserm.fr

                This article was submitted to Frontiers in Cellular Endocrinology, a specialty of Frontiers in Endocrinology.

                Article
                DOI: 10.3389/fendo.2011.00002
                PMC ID: 3355952
                PubMed ID: 22649357
                SO-VID: 73526ad1-49b2-4ef8-a678-ddf8183fb01c
                Copyright © Copyright © 2011 Kamal and Jockers.
                License:

                This is an open-access article subject to an exclusive license agreement between the authors and Frontiers Media SA, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are credited.

                History
                Date received : 27 November 2010
                Date accepted : 13 January 2011
                Page count
                Figures: 3, Tables: 1, Equations: 0, References: 128, Pages: 14, Words: 13454
                Categories
                Subject: Endocrinology
                Subject: Review Article

                ScienceOpen disciplines: Endocrinology & Diabetes
                Keywords: functional crosstalk,endocrinology,direct physical interaction,heterodimers,gpcr
                Data availability:
                ScienceOpen disciplines: Endocrinology & Diabetes
                Keywords: functional crosstalk, endocrinology, direct physical interaction, heterodimers, gpcr

                Comments

                Comment on this article

                scite_

                Similar content338

                See all similar

                Cited by11

                See all cited by

                Most referenced authors1,337

                See all reference authors