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The asymmetric / symmetric activation of GPCR dimers as a possible mechanistic rationale for multiple signalling pathways

Reference: Trends Pharmacol Sci. 2010 Jan;31(1):15-21 The asymmetric / symmetric activation of GPCR dimers as a possible mechanistic rationale for multiple signalling pathways
Authors: Xavier Rovira (1), Jean-Philippe Pin (2) and Jesús Giraldo (1)
1- Laboratory of Systems Pharmacology and Bioinformatics, Institut de Neurociencies and Unitat de Bioestadıstica, Universitat Autonoma de Barcelona, 08193 Bellaterra, Spain.
2- CNRS,UMR 5203, Institut de Genomique fonctionnelle, Montpellier, France and INSERM, U661, Montpellier, France and Universite Montpellier 1 and 2, Montpellier, France.
Summary: G protein-coupled receptors (GPCRs) represent the major target for drug development. Although these receptors can activate their cognate G-proteins in a monomeric form, it is now recognized that they can assemble into dimers, or larger oligomers. However, the functional consequences of such receptor assembly remain elusive. Recent data revealed an 'asymmetric' organization of some dimers when activating heterotrimeric G-proteins, while a symmetric organization may be required for the activation of other signalling pathways. Here we describe a mathematical model taking these latest ideas into consideration, and report on the expected consequences of the activation of different signalling pathways. This model helps clarify data already published, and will certainly be helpful to further explain the functional significance of GPCR oligomerization. It may help develop more specific drugs targeting a specific signalling cascade.
Description:

Imagen artículo Febrero


REFERENCIA DEL GRUPO Y/O INVESTIGADOR
Xavier Rovira se encuentra en su último año de tesis dentro del grupo de investigación del Dr. Jesús Giraldo. El Laboratorio de Farmacología de Sistemas y Bioinformática (Instituto de Neurociencias, Universidad Autónoma de Barcelona) es un equipo interdisciplinario compuesto por químicos, biólogos, informáticos y matemáticos. El grupo ha desarrollado nuevas metodologías combinando modelización matemática y molecular para el estudio de la interacción ligando-receptor y la transducción de señales


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