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http://hdl.handle.net/2445/120405
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DC Field | Value | Language |
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dc.contributor.author | Navarro Brugal, Gemma | - |
dc.contributor.author | Aguinaga Andrés, David | - |
dc.contributor.author | Angelats Canals, Edgar | - |
dc.contributor.author | Medrano Moya, Mireia | - |
dc.contributor.author | Moreno Guillén, Estefanía | - |
dc.contributor.author | Mallol Montero, Josefa | - |
dc.contributor.author | Cortés Tejedor, Antonio | - |
dc.contributor.author | Canela Campos, Enric I. | - |
dc.contributor.author | Casadó, Vicent | - |
dc.contributor.author | McCormick, Peter J. | - |
dc.contributor.author | Lluís i Biset, Carme | - |
dc.contributor.author | Ferré, Sergi | - |
dc.date.accessioned | 2018-03-02T15:24:33Z | - |
dc.date.available | 2018-03-02T15:24:33Z | - |
dc.date.issued | 2016-04-25 | - |
dc.identifier.issn | 0021-9258 | - |
dc.identifier.uri | http://hdl.handle.net/2445/120405 | - |
dc.description.abstract | The truncated non-signaling ghrelin receptor GHS-R1b has been suggested to simply exert a dominant negative role in the trafficking and signaling of the full and functional ghrelin receptor GHS-R1a. Here we reveal a more complex modulatory role of GHS-R1b. Differential co-expression of GHS-R1a and GHS-R1b, both in HEK-293T cells and in striatal and hippocampal neurons in culture, demonstrates that GHS-R1b acts as a dual modulator of GHS-R1a function: low relative GHS-R1b expression potentiates and high relative GHS-R1b expression inhibits GHS-R1a function by facilitating GHS-R1a trafficking to the plasma membrane and by exerting a negative allosteric effect on GHS-R1a signaling, respectively. We found a preferential Gi/o-coupling of the GHS-R1a-GHS-R1b complex in HEK-293T cells and, unexpectedly, a preferential Gs/olf coupling in both striatal and hippocampal neurons in culture. A dopamine D1 receptor (D1R) antagonist blocked ghrelin-induced cAMP accumulation in striatal but not hippocampal neurons, indicating the involvement of D1R in the striatal GHS-R1a-Gs/olf coupling. Experiments in HEK-293T demonstrated that D1R co-expression promotes a switch in GHS-R1a-G protein coupling, from Gi/o to Gs/olf, but only upon co-expression of GHS-R1b. Furthermore, resonance energy transfer experiments showed that D1R interacts with GHS-R1a, but only in the presence of GHS-R1b. Therefore, GHS-R1b not only determines the efficacy of ghrelin-induced GHS-R1a-mediated signaling, but also determines the ability of GHS-R1a to form oligomeric complexes with other receptors promoting profound qualitative changes in ghrelin-induced signaling. | - |
dc.format.extent | 15 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | American Society for Biochemistry and Molecular Biology | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1074/jbc.M116.715144 | - |
dc.relation.ispartof | Journal of Biological Chemistry, 2016, vol. 291, p. 13048-13062 | - |
dc.relation.uri | https://doi.org/10.1074/jbc.M116.715144 | - |
dc.rights | (c) American Society for Biochemistry and Molecular Biology, 2016 | - |
dc.source | Articles publicats en revistes (Bioquímica i Biomedicina Molecular) | - |
dc.subject.classification | Oligòmers | - |
dc.subject.classification | Dopamina | - |
dc.subject.classification | Proteïnes | - |
dc.subject.classification | Receptors cel·lulars | - |
dc.subject.other | Oligomers | - |
dc.subject.other | Dopamine | - |
dc.subject.other | Proteins | - |
dc.subject.other | Cell receptors | - |
dc.title | Significant Role of the Truncated Ghrelin Receptor GHS-1Rb in Ghrelin-Induced Signaling in Neurons | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 662375 | - |
dc.date.updated | 2018-03-02T15:24:33Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 27129257 | - |
Appears in Collections: | Articles publicats en revistes (Bioquímica i Fisiologia) Articles publicats en revistes (Bioquímica i Biomedicina Molecular) |
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File | Description | Size | Format | |
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662375.pdf | 3.39 MB | Adobe PDF | View/Open |
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