Les protéines Arf : transport membranaire, morphologie épithéliale et cancer – IPMC

Recherche

Intranet

Thème

Transport de lipides : mécanismes moléculaires et rôle dans la pathogenèse

Métabolisme et fonctions des lipides membranaires

Membres

Frédéric LUTON

Chercheur INSERM

Sarah COGOLUEGNES

Laetitia DELLA-CROCE

Enseignant-chercheur UniCA

Isabelle MUS-VETEAU

Présentation

Schématiquement, la morphologie cellulaire repose sur la membrane plasmique qui forme une enveloppe lipidique à l’intérieur de laquelle le cytosquelette d’actine, un échafaudage moléculaire modulable, structure la forme des cellules. La morphologie cellulaire ainsi que l’arrangement intracellulaire des organelles et des cytosquelettes (actine, microtubules, filaments intermédiaires) sont adaptés au service des multiples fonctions cellulaires telles que le transport vésiculaire, la sécrétion, la phagocytose, l’adhésion, la migration, etc. Les cellules assemblent également des sous-structures membranaires de surface (cil, filopodes, lamellipodes, spicules, CDR, etc) qui leur confèrent des propriétés particulières. Ainsi, l’organisation coordonnée et dynamique de la membrane plasmique et du cytosquelette d’actine est un élément clé du bon fonctionnement des cellules de l’organisme.
La petite protéine G Arf6, ses régulateurs et ses effecteurs sont impliqués dans l’architecture cellulaire et dans de nombreux processus nécessitant un remodelage de la morphologie cellulaire. Ces dernières années nous avons focalisé nos recherches sur leur rôle dans l’organisation du cytosquelette d’actine et le trafic membranaire, la polarité épithéliale et le cancer, et enfin la recherche de drogues anti-cancéreuses.

Projets

Drogues anti-cancéreuses

Dans le laboratoire, nous développons deux types de drogues anti-cancéreuses : des inhibiteurs de l’invasion tumorale dépendante d’Arf6 et des […]

Polarité épithéliale et cancer

Les tissus épithéliaux tapissent la face interne des organes. Ils sont formés de cellules polarisées présentant un domaine apical ouvert […]

Transport membranaire et cytosquelette d’actine

► Les petites protéines G Arf sont impliquées dans le transport intracellulaire mais leur fonction exacte demeure encore mal définie. […]

Publications

Kovachka S, Malloci G, Simsir M, Ruggerone P, Azoulay S, Mus-Veteau I, Inhibition of the drug efflux activity of Ptch1 as a promising strategy to overcome chemotherapy resistance in cancer cells., Eur J Med Chem 2022 Jun; 236(): 114306.

Álvaro Javier Feliz Morel, Anida Hasanovic, Aurélie Morin, Chloé Prunier, Virginie Magnone, Kevin Lebrigand, Amaury Aouad, Sarah Cogoluegnes, Judith Favier, Claude Pasquier, Isabelle Mus-Veteau, Persistent Properties of a Subpopulation of Cancer Cells Overexpressing the Hedgehog Receptor Patched, Pharmaceutics, 2022, 14 (5), pp.988. ⟨10.3390/pharmaceutics14050988⟩.

Feliz Morel ÁJ, Hasanovic A, Morin A, Prunier C, Magnone V, Lebrigand K, Aouad A, Cogoluegnes S, Favier J, Pasquier C, Mus-Veteau I, Persistent Properties of a Subpopulation of Cancer Cells Overexpressing the Hedgehog Receptor Patched., Pharmaceutics 2022 May; 14(5): .

Álvaro Javier Feliz Morel, Anida Hasanovic, Aurélie Morin, Chloé Prunier, Virginie Magnone, Kevin Lebrigand, Amaury Aouad, Sarah Cogoluegnes, Judith Favier, Claude Pasquier, Isabelle Mus-Veteau, Persistent Properties of a Subpopulation of Cancer Cells Overexpressing the Hedgehog Receptor Patched, Pharmaceutics, 2022, 14 (5), pp.988. ⟨10.3390/pharmaceutics14050988⟩.

Kovachka S, Soule P, Mus-Veteau I, Microscale Thermophoresis to Evaluate the Functionality of Heterologously Overexpressed Membrane Proteins in Membrane Preparations., Methods Mol Biol 2022 ; 2507(): 445-461.

Marcetteau J, Matusek T, Luton F, Thérond PP, Arf6 is necessary for senseless expression in response to wingless signalling during Drosophila wing development., Biol Open 2021 Dec; 10(12): .

Fayad R, Rojas MV, Partisani M, Finetti P, Dib S, Abelanet S, Virolle V, Farina A, Cabaud O, Lopez M, Birnbaum D, Bertucci F, Franco M, Luton F, EFA6B regulates a stop signal for collective invasion in breast cancer., Nat Commun 2021 Apr; 12(1): 2198.

Kovachka S, Malloci G, Vargiu AV, Azoulay S, Mus-Veteau I, Ruggerone P, Molecular insights into the Patched1 drug efflux inhibitory activity of panicein A hydroquinone: a computational study., Phys Chem Chem Phys 2021 Apr; 23(13): 8013-8022.

Durand N, Simsir M, Signetti L, Labbal F, Ballotti R, Mus-Veteau I, Methiothepin Increases Chemotherapy Efficacy against Resistant Melanoma Cells., Molecules 2021 Mar; 26(7): .

Simsir M, Broutin I, Mus-Veteau I, Cazals F, Studying dynamics without explicit dynamics: A structure-based study of the export mechanism by AcrB., Proteins 2021 Mar; 89(3): 259-275.

Macia E, Vazquez-Rojas M, Robiolo A, Fayad R, Abélanet S, Mus-Veteau I, Fontaine-Vive F, Mehiri M, Luton F, Franco M, Chlortetracycline, a Novel Arf Inhibitor That Decreases the Arf6-Dependent Invasive Properties of Breast Cancer Cells., Molecules 2021 Feb; 26(4): .

Partisani M, Baron CL, Ghossoub R, Fayad R, Pagnotta S, Abélanet S, Macia E, Brau F, Lacas-Gervais S, Benmerah A, Luton F, Franco M, EFA6A, an exchange factor for Arf6, regulates early steps in ciliogenesis., J Cell Sci 2021 Jan; 134(2): .

Daniel Klionsky, Amal Kamal Abdel-Aziz, Sara Abdelfatah, Mahmoud Abdellatif, Asghar Abdoli, Steffen Abel, Hagai Abeliovich, Marie Abildgaard, Yakubu Princely Abudu, Abraham Acevedo-Arozena, Iannis Adamopoulos, Khosrow Adeli, Timon Adolph, Annagrazia Adornetto, Elma Aflaki, Galila Agam, Anupam Agarwal, Bharat Aggarwal, Maria Agnello, Patrizia Agostinis, Javed Agrewala, Alexander Agrotis, Patricia Aguilar, S. Tariq Ahmad, Zubair Ahmed, Ulises Ahumada-Castro, Sonja Aits, Shu Aizawa, Yunus Akkoc, To..., Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition), Autophagy, 2021, 17 (1), pp.1-382. ⟨10.1080/15548627.2020.1797280⟩.

Hasanovic A, Simsir M, Choveau FS, Lalli E, Mus-Veteau I, Astemizole Sensitizes Adrenocortical Carcinoma Cells to Doxorubicin by Inhibiting Patched Drug Efflux Activity., Biomedicines 2020 Jul; 8(8): .

Macia E, Partisani M, Wang H, Lacas-Gervais S, Le Clainche C, Luton F, Franco M, The C-terminal domain of EFA6A interacts directly with F-actin and assembles F-actin bundles., Sci Rep 2019 Dec; 9(1): 19209.

Hasanovic A, Mus-Veteau I, Targeting the Multidrug Transporter Ptch1 Potentiates Chemotherapy Efficiency., Cells 2018 Aug; 7(8): .

Hasanovic A, Ruggiero C, Jung S, Rapa I, Signetti L, Ben Hadj M, Terzolo M, Beuschlein F, Volante M, Hantel C, Lalli E, Mus-Veteau I, Targeting the multidrug transporter Patched potentiates chemotherapy efficiency on adrenocortical carcinoma in vitro and in vivo., Int J Cancer 2018 Jul; 143(1): 199-211.

Milanini J, Fayad R, Partisani M, Lecine P, Borg JP, Franco M, Luton F, EFA6 proteins regulate lumen formation through α-actinin 1., J Cell Sci 2018 Feb; 131(3): .

Fiorini L, Mus-Veteau I, Method to Screen Multidrug Transport Inhibitors Using Yeast Overexpressing a Human MDR Transporter., Methods Mol Biol 2016 ; 1432(): 303-18.

Fiorini L, Tribalat MA, Sauvard L, Cazareth J, Lalli E, Broutin I, Thomas OP, Mus-Veteau I, Natural paniceins from mediterranean sponge inhibit the multidrug resistance activity of Patched and increase chemotherapy efficiency on melanoma cells., Oncotarget 2015 Sep; 6(26): 22282-97.

Treuner-Lange A, Macia E, Guzzo M, Hot E, Faure LM, Jakobczak B, Espinosa L, Alcor D, Ducret A, Keilberg D, Castaing JP, Lacas Gervais S, Franco M, Søgaard-Andersen L, Mignot T, The small G-protein MglA connects to the MreB actin cytoskeleton at bacterial focal adhesions., J Cell Biol 2015 Jul; 210(2): 243-56.

Figeac F, Dagouassat M, Mahrouf-Yorgov M, Le Gouvello S, Trébeau C, Sayed A, Stern JB, Validire P, Dubois-Randé JL, Boczkowski J, Mus-Veteau I, Rodriguez AM, Lung fibroblasts share mesenchymal stem cell features which are altered in chronic obstructive pulmonary disease via the overactivation of the Hedgehog signaling pathway., PLoS One 2015 ; 10(3): e0121579.

Mus-Veteau I, Lambeau G, Special issue: from membranes to pathologies., Biochimie 2014 Dec; 107 Pt A(): 1-2.

Zangari J, Partisani M, Bertucci F, Milanini J, Bidaut G, Berruyer-Pouyet C, Finetti P, Long E, Brau F, Cabaud O, Chetaille B, Birnbaum D, Lopez M, Hofman P, Franco M, Luton F, EFA6B antagonizes breast cancer., Cancer Res 2014 Oct; 74(19): 5493-506.

Boulakirba S, Macia E, Partisani M, Lacas-Gervais S, Brau F, Luton F, Franco M, Arf6 exchange factor EFA6 and endophilin directly interact at the plasma membrane to control clathrin-mediated endocytosis., Proc Natl Acad Sci U S A 2014 Jul; 111(26): 9473-8.

Lalli E, Doghman M, Latre de Late P, El Wakil A, Mus-Veteau I, Beyond steroidogenesis: novel target genes for SF-1 discovered by genomics., Mol Cell Endocrinol 2013 May; 371(1-2): 154-9.

Bidet M, Tomico A, Martin P, Guizouarn H, Mollat P, Mus-Veteau I, The Hedgehog receptor patched functions in multidrug transport and chemotherapy resistance., Mol Cancer Res 2012 Nov; 10(11): 1496-508.

Hovers J, Potschies M, Polidori A, Pucci B, Raynal S, Bonneté F, Serrano-Vega MJ, Tate CG, Picot D, Pierre Y, Popot JL, Nehmé R, Bidet M, Mus-Veteau I, Busskamp H, Jung KH, Marx A, Timmins PA, Welte W, A class of mild surfactants that keep integral membrane proteins water-soluble for functional studies and crystallization., Mol Membr Biol 2011 Apr; 28(3): 171-81.

Bidet M, Joubert O, Lacombe B, Ciantar M, Nehmé R, Mollat P, Brétillon L, Faure H, Bittman R, Ruat M, Mus-Veteau I, The hedgehog receptor patched is involved in cholesterol transport., PLoS One 2011 ; 6(9): e23834.

Nehmé R, Mus-Veteau I, Proteins of the Hedgehog signaling pathway as therapeutic targets against cancer., Expert Rev Proteomics 2010 Aug; 7(4): 601-12.

Nehmé R, Joubert O, Bidet M, Lacombe B, Polidori A, Pucci B, Mus-Veteau I, Stability study of the human G-protein coupled receptor, Smoothened., Biochim Biophys Acta 2010 Jun; 1798(6): 1100-10.

Joubert O, Nehmé R, Bidet M, Mus-Veteau I, Heterologous expression of human membrane receptors in the yeast Saccharomyces cerevisiae., Methods Mol Biol 2010 ; 601(): 87-103.

Mus-Veteau I, Heterologous expression of membrane proteins for structural analysis., Methods Mol Biol 2010 ; 601(): 1-16.

Joubert O, Nehmé R, Fleury D, De Rivoyre M, Bidet M, Polidori A, Ruat M, Pucci B, Mollat P, Mus-Veteau I, Functional studies of membrane-bound and purified human Hedgehog receptor Patched expressed in yeast., Biochim Biophys Acta 2009 Sep; 1788(9): 1813-21.

De Rivoyre M, Ruel L, Varjosalo M, Loubat A, Bidet M, Thérond P, Mus-Veteau I, Human receptors patched and smoothened partially transduce hedgehog signal when expressed in Drosophila cells., J Biol Chem 2006 Sep; 281(39): 28584-95.

Pisani DF, Rivoyre MD, Ruel L, Bonino F, Bidet M, Dechesne CA, Mus-Veteau I, Mouse myodulin, a new potential angiogenic factor, functionally expressed in yeast., Biochem Biophys Res Commun 2005 Jun; 331(2): 552-6.

De Rivoyre M, Bonino F, Ruel L, Bidet M, Thérond P, Mus-Veteau I, Human receptor Smoothened, a mediator of Hedgehog signalling, expressed in its native conformation in yeast., FEBS Lett 2005 Feb; 579(6): 1529-33.

Luton F, Klein S, Chauvin JP, Le Bivic A, Bourgoin S, Franco M, Chardin P, EFA6, exchange factor for ARF6, regulates the actin cytoskeleton and associated tight junction in response to E-cadherin engagement., Mol Biol Cell 2004 Mar; 15(3): 1134-45.

Mus-Veteau I, Heterologous expression and purification systems for structural proteomics of mammalian membrane proteins., Comp Funct Genomics 2002 ; 3(6): 511-7.

Dave N, Troullier A, Mus-Veteau I, Duñach M, Leblanc G, Padrós E, Secondary structure components and properties of the melibiose permease from Escherichia coli: a fourier transform infrared spectroscopy analysis., Biophys J 2000 Aug; 79(2): 747-55.

Cordat E, Leblanc G, Mus-Veteau I, Evidence for a role of helix IV in connecting cation- and sugar-binding sites of Escherichia coli melibiose permease., Biochemistry 2000 Apr; 39(15): 4493-9.

Cordat E, Mus-Veteau I, Leblanc G, Structural studies of the melibiose permease of Escherichia coli by fluorescence resonance energy transfer. II. Identification of the tryptophan residues acting as energy donors., J Biol Chem 1998 Dec; 273(50): 33198-202.

Maehrel C, Cordat E, Mus-Veteau I, Leblanc G, Structural studies of the melibiose permease of Escherichia coli by fluorescence resonance energy transfer. I. Evidence for ion-induced conformational change., J Biol Chem 1998 Dec; 273(50): 33192-7.

Mus-Veteau I, Leblanc G, Melibiose permease of Escherichia coli: structural organization of cosubstrate binding sites as deduced from tryptophan fluorescence analyses., Biochemistry 1996 Sep; 35(37): 12053-60.

Poolman B, Knol J, van der Does C, Henderson PJ, Liang WJ, Leblanc G, Pourcher T, Mus-Veteau I, Cation and sugar selectivity determinants in a novel family of transport proteins., Mol Microbiol 1996 Mar; 19(5): 911-22.

Mus-Veteau I, Pourcher T, Leblanc G, Melibiose permease of Escherichia coli: substrate-induced conformational changes monitored by tryptophan fluorescence spectroscopy., Biochemistry 1995 May; 34(20): 6775-83.

Mus-Veteau I, Guerlesquin F, Involvement of histidine residues in the catalytic mechanism of hydrogenases., Biochem Biophys Res Commun 1994 May; 201(1): 128-34.

Mus-Veteau I, Dolla A, Guerlesquin F, Payan F, Czjzek M, Haser R, Bianco P, Haladjian J, Rapp-Giles BJ, Wall JD, Site-directed mutagenesis of tetraheme cytochrome c3. Modification of oxidoreduction potentials after heme axial ligand replacement., J Biol Chem 1992 Aug; 267(24): 16851-8.

I. Mus-Veteau, A. Dolla, F. Guerlesquin, F. Payan, M. Czjzek, R. Haser, P. Bianco, J. Haladjian, Bj Rapp-Giles, Jd Wall, Site-directed mutagenesis of tetraheme cytochrome c3. Modification of oxidoreduction potentials after heme axial ligand replacement., Journal of Biological Chemistry, 1992, 267, pp.16851-16858.

I. Mus-Veteau, G. Chottard, O. Lexa, Françoise Guerlesquin, Mireille Bruschi, Cytochrome c3-heteropolytungstate complex, a model for the interaction of the tetrahemic cytochrome with its redox partners: ferredoxin and rubredoxin, BBA - Biochimica et Biophysica Acta, 1992, 1102, pp.353.

I. Mus-Veteau, A. Dolla, Françoise Guerlesquin, F. Payan, M. Czjzek, R. Haser, P. Bianco, J. Haladjian, B. Rapp-Giles, B. Wall, G. Voordoum, Mireille Bruschi, Site directed mutagenesis of tetraheme cytochrome c3: modification of redox potentials after heme axial ligand replacement, Journal of Biological Chemistry, 1992, 267, pp.16851.