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Oligomérisation des récepteurs couplés aux protéines G : deux ou plus ? Application des technologies de FRET en temps résolu au cas du récepteur GABAB

Abstract : G protein-coupled receptors (GPCR) are the target of 50% of the drugs on the pharmaceutical market at present. Therefore, understanding their function is essential for the development of new molecules capable of targeting these receptors. This last decade, FRET technologies have enabled the understanding of how GPCR, considered as monomers for a long time, gather together into dimers or larger oligomeric structures.
However, the precise characterization of this stœchiometry entails the development of adapted methods. During this work, we developed a time-resolved FRET approach allowing to observe, by using labeled antibodies, GPCR subunit interactions on the surface of living cells. This approach enabled us to reveal the homo- and heterodimerization of this receptor at the cell surface. As cells were permeabilized, oligomerization of GABAB1 subunits retained in the intracellular compartments could be characterized by the same approach.
In order to analyse more precisely the organization of the GABAB receptor, we developed a second method to irreversibly label with fluorophores the GABAB1 and GABAB2 subunits present at the cell surface. The combination of this labeling method with a time-resolved FRET analysis allowed the characterization of the oligomeric organization of this receptor. Thus, the GABAB receptor, known as an obligatory heterodimer, seems to be able to form oligomers through the GABAB1 subunit which represents a point of contact between two heterodimers. The impact of such an organization on the function of this receptor remains to determine.
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https://tel.archives-ouvertes.fr/tel-00165100
Contributor : Damien Maurel <>
Submitted on : Tuesday, July 24, 2007 - 4:21:37 PM
Last modification on : Wednesday, October 14, 2020 - 3:57:28 AM
Long-term archiving on: : Friday, November 25, 2016 - 5:44:04 PM

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  • HAL Id : tel-00165100, version 1

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Damien Maurel. Oligomérisation des récepteurs couplés aux protéines G : deux ou plus ? Application des technologies de FRET en temps résolu au cas du récepteur GABAB. Biologie cellulaire. Université Montpellier I, 2006. Français. ⟨tel-00165100⟩

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