Research Description:
Our lab focuses on the mechanisms that control hormonal responses mediated by G protein-coupled receptors (GPCRs). Our chief goal is to understand how changes in signaling networks for these receptors affect their own responsiveness. We use cellular imaging approaches such as confocal microscopy to study in real time how the dynamics of signaling complexes affects the desensitization, internalization and intracellular trafficking of receptors. Another aspect of our research involves the development and characterization of “bias agonists” in the regulation of receptor signaling, with the goal of developing new therapeutic modalities for receptor-related diseases such as hypertension, nephrogenic diabetes insipidus, infection, inflammation and cancer.
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Selected Publications:
Hamdan FF, Rochdi, MD, Breton B, Fessart D, Michaud DE, Charest PG, Laporte SA and Bouvier M. Unraveling g protein-coupled receptor endocytosis pathways using real-time monitoring ofagonist-promoted interaction between ß-arrestins and AP-2. J Biol Chem. 2007; 282(40):29089-100.
Fessart D, Simaan M, Zimmerman B, Comeau L, Hamdam FF, Wiseman PW, Bouvier M and Laporte SA. Src-dependent phosphorylation of beta2-adaptin dissociates the beta-arrestin-AP-2 complex. J Cell Sci. 2007 May 15;120(Pt 10):1723-32.
Gousseva V, Simaan M, Laporte SA, and Swain S. Inferring the lifetime of endosomal complexes by fluorescence recovery after photobleaching. Biophys. J. (in press).
Poupart M-E, Fessart D, Cotton M, Laporte SA, and Claing A. Afr6 regulates the Angiotensin II type 1 receptor endocytosis by controlling the recruitment of AP-2 and clathrin. Cell Signal, 2007. 19(11):2370-8.
Claing A. and Laporte SA. Novel roles for arrestins in GPCR biology and drug discovery. Curr Opin Drug Dis. & Develop. 2005 8(5):585-9.
Ho J., Cocolakis E., Dumas VM, Posner BI, Laporte SA, Lebrun JJ. The G protein-coupled receptor kinase-2 is a TGFß-inducible antagonist of TGFß signal transduction. EMBO J., 2005 24(18): 3274-58.
Simaan M, Bedard-Goulet S, Fessart D, Gratton JP, Laporte SA. Dissociation of beta-arrestin from internalized bradykinin B2 receptor is necessary for receptor recycling and resensitization. Cell Signal. 2005 Sep;17(9):1074-83.
Fessart D, Simaan M, Laporte SA. c-Src regulates clathrin adapter protein 2 interaction with beta-arrestin and the angiotensin II type 1 receptor during clathrin- mediated internalization. Mol Endocrinol. 2005 Feb;19(2):491-503.
Hasbi A, Devost D, Laporte SA, Zingg HH. Real-time detection of interactions between the human oxytocin receptor and G protein-coupled receptor kinase-2. Mol Endocrinol. 2004 May;18(5):1277-86.
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