Accueil > UMR 7242 Biotechnologie et signalisation cellulaire (Jean-Luc Galzi) > Récepteurs, protéines membranaires et innovation thérapeutique (Animation scientifique : Isabelle Schalk) > RCPG, douleur et inflammation (Frédéric Simonin) > Nos thématiques > GASP-1
Implication of GASP-1 in the adaptations to chronic stimulation of GPCRs and pain
At the cellular level, chronic stimulation of GPCRs is accompanied with a variety of regulatory processes that tend to decrease the cellular response, usually referred to as desensitization. Short- and long-term desensitization mechanisms have been described. We have recently identified a novel protein family, termed “G protein-coupled receptor Associated Sorting Proteins” or GASPs, which interact with a broad range of GPCRs and are thought to modulate both receptor intracellular trafficking and degradation following agonist stimulation (Simonin et al. 2004 ; Abu-Helo and Simonin 2010). Moreover, it has been recently reported that GASP-1 may also interacts with other intracellular partners (Per1, BARD-1 ; (Goehler et al. 2004)), suggesting additional functions for this protein in connection (or not) with the activation of different GPCRs. We have generated GASP-1 KO mice and shown that responses to overstimulation of dopamine receptors are modified compared to those of WT animals (Boeuf et al. 2009). More recently, Martini and collaborators have shown that the development of analgesic tolerance upon chronic administration of a cannabinoid CB1 receptor agonist is attenuated in those animals (Martini et al. 2010).
Overall, these observations suggest that GASP-1 plays an important role in adaptive responses to chronic stimulation of many GPCRs. However, the cellular and molecular functions of this protein are still largely unknown.
In the project, we will investigate the role of GASP-1, using various techniques ranging from molecular and cellular biology to behavioural studies on whole animals.
The GASP family.
The percentage of identical amino acids shared with GASP-1 is indicated within each box corresponding to the conserved C-terminal domain of GASPs. Bold black lines represent the conserved motif of 15 amino acids found in GASP-1 to -5. Bold grey lines represent repeated motifs that do not perfectly match the consensus sequence. Broken lines represent putative transmembrane domains. Parallel rectangles with small capital A represent putative armadillo repeats.
Simonin et al, 2004, J. Neurochem. 89, 766-75
Goehler et al, 2004, Mol. Cell 15, 853-865
Boeuf et al, 2009, European. J. Neurosci. 30, 860-868
Abu Helo and Simonin, 2010, Pharmacol. Ther. 126, 244-250
Martini et al, 2010, Neuropsychopharmacology 35, 1363-1373