Team leader:
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Stefano Marullo |
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CV Science, Aviesan
Research Gate
The communication between the cells in the body passes through the activation of molecular switches known as receptors. In response to external chemical or physical signals, receptors stimulate a series of molecular partners capable of propagating a biochemical signal inside the cels. Ultimately, this signal elicits a cellular response, which is adapted to the external signal. Our team focuses on the regulation of receptors and on the organization of molecular scaffolds that carry their signals, under either normal operating conditions or during various diseases. |
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G protein coupled receptors (GPCRs), the largest family of membrane receptors, are implicated in a wide range of human diseases. Signal outputs resulting from their activation depend on their subcellular location and on their local interacting partners, among which beta-arrestins (barrs) play a major role. Our project focuses on emerging paradigms of regulated GPGR and barr subcellular trafficking, from mechanistic molecular aspects to physiology and pathology.
The principal specific aims of our project are (Project Leaders):
-Deciphering cellular and molecular mechanisms involved in regulated GPCR export to the cell surface; pathophysiological implications (S Marullo)
-Investigating molecular basis of the interaction between pathogens and receptors for cell adhesion and signaling (S Marullo)
-Exploring mechanisms and functions of the nuclear trafficking of the regulatory scaffolding proteins barrs (H Enslen, M Scott)
-Deciphering new GPCR/barr-dependent mechanisms that regulate cell adhesion (H Enslen)
-Studying GPCR/barr-dependent mechanisms that regulate the anti-oncogenic PTEN phosphatase functions (M Scott)
Doly S., Shirvani H., Gäta G., Meye F., Emerit M.B., Enslen H., Achour L., Pardo-Lopez L., Seung-Kwon Y., Armand V., Gardette R., Giros B., Gassmann M., Bettler B., Mameli M., Darmon M. and Marullo S. GABAB receptor cell surface export is controlled by an endoplasmic reticulum gatekeeper. Mol. Psychiatry 2016 21:480-90
Paradis J.S., Ly S., Blondel-Tepaz E., Galan J.A., Beautrait A., Scott M.G.H., Enslen H., Marullo S., Roux P.P., Bouvier M. Receptor sequestration in response to βarrestin-2 phosphorylation governs steady-state levels of GPCR cell surface expression. Proc Natl Acad Sci USA 112:E5160-E5168 (2015).
Lima-Fernandes E, Misticone S, Boularan C, Paradis JS, Enslen H, Roux PP, Bouvier M, Baillie GS, Marullo S, Scott MG A biosensor to monitor dynamic regulation and function of tumour suppressor PTEN in living cells. Nat Commun. 2014 5:4431.
Bernard SC, Simpson N, Join-Lambert O, Federici C, Laran-Chich MP, Maïssa N, Bouzinba-Ségard H, Morand PC, Chretien F, Taouji S, Chevet E, Janel S, Lafont F, Coureuil M, Segura A, Niedergang F, Marullo S, Couraud PO, Nassif X, Bourdoulous S. Pathogenic Neisseria meningitidis utilizes CD147 for vascular colonization. Nat Med. 2014 20:725-731.
Lima-Fernandes E, Enslen H, Camand E, Kotelevets L, Boularan C, Achour L, Benmerah A, Gibson LC, Baillie GS, Pitcher JA, Chastre E, Etienne-Manneville S, Marullo S, Scott MG. Distinct functional outputs of PTEN signalling are controlled by dynamic association with β-arrestins. EMBO J. 2011 30:2557-2568.
Achour L, Kamal M, Jockers R, Marullo S. Using quantitative BRET to assess G protein-coupled receptor homo- and heterodimerization. Methods Mol Biol. 2011 756:183-200.
Coureuil M, Lécuyer H, Scott MG, Boularan C, Enslen H, Soyer M, Mikaty G, Bourdoulous S, Nassif X, Marullo S. Meningococcus Hijacks a β2-adrenoceptor/β-Arrestin pathway to cross brain microvasculature endothelium. Cell. 2010 143:1149-1160.
Obtained the label of Fondation pour la Recherche Médicale (FRM)-team in 2012
Member of the Labex «Who am I ?». Who am I? is a large, cooperative and multi-disciplinary research project focusing on the fundamental question of the basis of identity (http://www.labex-whoami.fr/en/who-am-i)
Member of the DHU (Département Hospitalo-Univestaire) AUTHORS «Maladies hormonales et auto-immunes» created in 2013
Member of the GDR (Groupe de Recherche) RCPG-Physio-Med. The GDR3545 on “G Protein-coupled Receptors : from physiology to drugs (RCPG-Physio-Med)” was created in 2012 by the CNRS (http://www.gdr3545.com)
EUROPE: N° 10306215.4 M. Coureuil, S. Marullo, X.Nassif: "Compounds for delivering a therapeutic or imaging agent to the brain". Janvier 2011.
Team projects are supported by:
Fondation pour la Recherche Médicale (FRM), 2012-2015
Institut National du Cancer (INCA) 2014-2016
Agence Nationale pour la Recherche (ANR) Programme Blanc 2015-2017
Ligue contre le Cancer 2014-2015
Vincenzo PIEROTTI
(LAB manager, 1997-2002) Investment Consultant, San Francisco, CA, USA
Hassan ISSAFRAS
(PhD, 1999-2003) Permanent position, Preclinical Research XOMA Corporation, Berkeley, CA, USA
Catherine LABBE-JULLIE (Senior Scientist, 1999-2007) Chargé de Mission, Vice Présidence Recherche, Université Paris Descartes
Hélène STOREZ
(PhD, 2004-2007) Medical Copywriter, DDB Health, Paris
Cédric BOULARAN
(PhD 2005-2009) Ingénieur de Recherche, Cardiovascular Diseases Institute (I2MC), Toulouse, France
Lamia ACHOUR
(Master2 degree and PhD, 2004-2010) Clinical study manager, TRIO (Translational Research in Oncology), Paris
Hamasseh SHIRVANI
(PhD, 2008-2011) Post Doctoral scientist, Istitut Curie, Orsay
Evelyne LIMA-FERNANDS
(Master2 degree and PhD, 2008-2012) Post Doctoral scientist, University of Toronto, Canada
Richard LEDUC
(Faculty of Medicine and Health Sciences, Université de Sherbrooke, Canada, 2010-2011)
Liliana PARDO-LOPEZ
(Instituto de Biotecnología, Universidad Nacional Autónoma de México, Mexique, 2009-2010)