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MOLECULAR MECHANISMS OF NEUROENDOCRINE SECRETION GROUP


Principal Investigator: Prof. Maite MONTERO, Ph.D.

 

Research areas

subcellular trafficking, secretory granule biogenesis,

neuroendocrine secretion disruption

Education and training

*M. Sc. in Populations Biology,

Pierre and Marie Curie University, Paris VI

*Ph.D. in Reproduction Physiology,

National Museum of Natural History, Paris VI

*Assistant professor, University of Rouen

*Habilitation à diriger des recherches (HDR)

Contact information

Inserm U1239 - DC2N Laboratory of Neuronal and

Neuroendocrine Communication and Differentiation

CURIB building, 2ndfloor, room 244

25, rue Tesnières 76821 Mont-Saint-Aignan

Telephone: +33(0)235 14 6643

E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

 

 

Research

 

 

Our researchactivityconcernsmolecularmechanismscontrolling (neuro)hormone secretion in physiological and pathophysiological conditions. Our group focus its attention on the identification of molecularactors  regulating the biogenesis of dense-coresecretory granules, organelles involved in the storing and release of (neuro)hormones in (neuro)endocrine cells. These organelles are generated by buddingfrom the trans-Golgi network membrane, a cellcompartmentwhereprotein (neuro)hormones are targeted to dense-coresecretory granules. Our studiesrevealed(i)that expression of the soluble proteinchromogranin A (CgA) in non-endocrine cellsinduced the formation of vesicular membrane surrounded structures sharing morphological and functionalcharacteristicswith dense-coresecretory granules, and (ii) that terminal regions of CgAwere crucial to hormone targeting (Montero-Hadjadje et al., 2009). Otherstudiesdemonstratedthatcytoskelettoninsures the trafficking of theseCgA-containingvesicular structures as itdoeswith dense-coresecretory granules (Elias et al., 2012) and thatacto-myosincomplexisinvolved in the biogenesis of secretory granules (Delacour-Delestre et al., 2017). Currentstudies are concentrated on the identification of molecularpartners of CgArequested at the TGN membrane to initiate the budding of dense-coresecretory granules. To achievethis goal, weestablished local (withchemist teams: Pr PY. RENARD, COBRA UMR 6014 CNRS; Dr S. ALEXANDRE, PBS UMR 6270 CNRS) and national (withbiochemists: Dr N. VITALE, UPR 3212 CNRS, Strasbourg ; withbiophysician: Dr D. MARGUET, CIML, Marseille) collaborations, and weobtainedgrantsfrom Région Normandie, France-Bioimaging network, Fondation pour la Recherche Médicale and Agence Nationale de la Recherche. We are currentlydevelopingmoleculartools (lipid probes), commerciallyunvailable and thatwillbeusedwithadvancedimaging techniques (TIRF and STED microscopyavailable on PRIMACEN, the Cell Imaging Plateform of our IRIB Institute; atomic force microscopyavailable in PBS laboratory; a microscope equippedwith a decaging system available in UPR 3212 CNRS; fluorescence correlativespectroscopyavailable in CIML, Marseille) to identify the role of CgA interaction with membrane lipidpartners in neurosecretion regulation in healthy and tumoral (neuro)endocrine cells.

 

Indeed, several (neuro)endocrine cancers are associated to a disrupted hormone secretionsuggesting an alteration of secretionmechanisms. Although a massive release of hormones iswellkown by clinicians in thispathologicalcontext, the molecularmechanismsleading to thisdysregulation are poorlyinvestigated. Then, the main goal of ourresearchis to identify the molecularmachinerycontrolling hormone secretion to understand the impact of secretoryactivity of tumoral (neuro)endocrine cells on the initiation and/or the evolution of (neuro)endocrine cancers  and to considerpotentialadaptedtherapeutical applications.

 

 

 

 Selected Publications

 

Carmon O, Laguerre F, Riachy L, Delestre-Delacour C, Wang Q, Tanguy E, Jeandel L, Cartier D, Thahouly T, Haeberlé AM, Fouillen L, Rezazgui O, Schapman D, Haefelé A, Goumon Y, Galas L, Renard PY, Alexandre S, Vitale N, Anouar Y, Montero-Hadjadje M. (2020) Chromogranin A preferential interaction with Golgi phosphatidic acid induces membrane deformation and contributes to secretory granule biogenesis. The  FASEB Journal 34:6769–6790.

 

Godefroy D, Boukhzar L, Dubessy C, Montero-Hadjadje M, Yon L, Eiden LE, Anouar Y. (2020) Three-dimensional mapping of tyrosine hydroxylase in the transparent brain and adrenal of prenatal and pre-weaning mice: Comprehensive methodological flowchart and quantitative aspects of 3D mapping. J Neurosci Methods 335:108596.

 

Laguerre F, Anouar Y, Montero-Hadjadje M. (2020) Chromogranin A in the early steps of the neurosecretory pathway. IUBMB Life 72:524-532.

 

Delestre-Delacour C, Carmon O, Laguerre F, Estay-Ahumada C, Courel M, Elias S, Jeandel L, Rayo MV, Peinado JR, Sengmanivong L, Gasman S, Coudrier E, Anouar Y, Montero-Hadjadje M. (2017) Myosin 1b and F-actin are involved in the control of secretory granule biogenesis. Scientific Reports 7:5172.

 

Carmon O, Laguerre F, Jeandel L, Anouar Y, Montero-Hadjadje M. (2017) Chromogranins as Molecular Coordinators at the Crossroads between Hormone Aggregation and Secretory Granule Biogenesis. In « Chromogranins: from Cell Biology to Physiology and Biomedicine », UNIPA Springer Series., 2017, pp 39-48.

 

Tanguy E, Carmon O, Wang Q, Jeandel L, Chasserot-Golaz S, Montero-Hadjadje M, Vitale N. (2016) Lipids implicated in the journey of a secretory granule: from biogenesis to fusion. Journal of Neurochemistry 137:904-12.

 

Courel M, El Yamani FZ, Alexandre D, El Fatemi H, Delestre C, Montero-Hadjadje M, Tazi F, Amarti A, Magoul R, Chartrel N, Anouar Y. (2014) Secretogranin II is overexpressed in advanced prostate cancer and promotes the neuroendocrine differentiation of prostate cancer cells. European Journal of Cancer, 50:3039-49.

 

Haissaguerre M, Courel M, Caron P, Denost S, Dubessy C, Gosse P, Appavoupoulle V, Belleannée G, Jullié ML, Montero-Hadjadje M, Yon L, Corcuff JB, Fagour C, Mazerolles C, Wagner T, Nunes ML, Anouar Y, Tabarin A. (2013) Normotensive incidentally discovered pheochromocytomas display specific biochemical, cellular, and molecular characteristics. Journal of Clinical Endocrinology and Metabolism, 98:4346-54.

 

Elias S., Delestre C., Ory S., Marais S., Courel M., Vazquez-Martinez R., Bernard S., Coquet L., Malagon M.M., Driouich A., Chan P., Gasman S., Anouar Y., Montero-Hadjadje M. (2012) Chromogranin A-induced granules interact with microtubules and actin filaments to establish a regulated secretory pathway. Endocrinology 153:4444-56.

 

Elias S., Delestre C., Courel M., Anouar Y., Montero-Hadjadje M. (2010) Chromogranin A as a crucial factor in the sorting of peptide hormones to secretory granules. Cellular and Molecular Neurobiology, 30:1189–1195.

 

Courel M., Soler-Jover A., Rodriguez-Flores J.L., Mahata S.K., Elias S., Montero-Hadjadje M., Anouar Y., Giuly R.J., O’Connor D.T., Taupenot L. (2010) The pro-hormone secretogranin II regulates dense-core secretory granule biogenesis in catecholaminergic cells. Journal of Biological Chemistry, 285:10030-43.

 

Montero-Hadjadje M., Elias S., Chevalier L., Benard M., Tanguy Y., Turquier V., Galas L., Yon L., Malagon M.M., Driouich A., Gasman S., Anouar Y. (2009) Chromogranin A promotes peptide hormone sorting to mobile granules in constitutively and regulated secreting cells: role of conserved N- and C-terminal peptides. Journal of Biological Chemistry, 284:12420-12431.

 

Montero-Hadjadje M., Vaingankar S., Elias S., Tostivint H., Mahata S.K., Anouar Y. (2008) Chromogranin A and B and secretogranin II: evolutionary and functional aspects. Acta Physiologica, 192:309-324.

 

Grumolato L., Ghzili H., Montero-Hadjadje M., Gasman S., Lesage J., Tanguy Y., Galas L., Ait-Ali D., Leprince J., Guérineau N.C., Elkahloun A.G., Fournier A., Vieau D., Vaudry H., Anouar Y. (2008) Selenoprotein T is a PACAP-regulated gene involved in intracellular Ca2+ mobilization and neuroendocrine secretion. The FASEB Journal, 22:1756-1768.

 

Guillemot J., Anouar Y., Montero-Hadjadje M., Grouzmann E., Grumolato L., Roshmaninho-Salgado J., Turquier V., Duparc C., Lefebvre H., Plouin P.F., Klein M.,  Muresan M., Chow B.K.C., Vaudry H., Yon L. (2006) Circulating EM66 is a highly sensitive marker for the diagnosis and follow-up of pheochromocytoma.International Journal of Cancer, 118:2003-2010.

 

 

Yon L., Guillemot J., Montero-Hadjadje M., Grumolato L., Leprince J., Lefebvre H., Contesse V., Plouin P.F., Vaudry H., Anouar Y. (2003) Identification of the secretogranin II-derived peptide EM66 in pheochromocytomas as a potential marker for discriminating benign versus malignant tumors. The Journal of Clinical Endocrinology and Metabolism, 88:2579-2585.

 

Montero-Hadjadje M., Pelletier G., Yon L., Li S., Guillemot J., Magoul R., Tillet Y., Vaudry H., Anouar Y. (2003) Biochemical characterization and immunocytochemical localization of EM66, a novel peptide derived from secretogranin II, in the rat pituitary and adrenal glands. The Journal of Histochemistry and Cytochemistry, 51:1083-1095.

 

 

 


 

Techniques and experimental models

 

*Primary culture of bovine chromaffin cells, neuroendocrine cell lines (COS7-CgA, PC12)

*Xenografts in nude mice

*Liposomes, Giant Unilamellar Vesicles

.

 *Immunocytochemistry, histology, cell transfection (lipidic agents, electroporation, virus)

*Microscopy (wild field, confocal, total internal reflection fluorescence,

time-lapse videomicroscopy, atomic force, light sheet, gated-STED)

*Radioimmunological assay, Western-Blot

 

*ARN interference

*Cloning and subcloning, directed mutagenesis

*PCR, RT-PCR, ADN preparation

 *Synthesis of recombinant proteins

 

 

 Collaborations

 

*Dr Stéphane Gasman et Dr Nicolas Vitale, Institut des Neurosciences Cellulaires et Intégratives, UPR 3212 CNRS Traficmembranairedans les cellules du systèmenerveux, Université de Strasbourg

*Dr Evelyne Coudrier, Institut Curie, UMR 144 CNRS Compartimentation et dynamiquecellulaires, Paris

*Pr Pierre-Yves Renard, Chimie Organique et Bioorganique : Réactivité et Analyse (COBRA), UMR 6014 CNRS, Université de Rouen

*Dr Stéphane Alexandre, Polymères-Bioplymères-Surfaces (PBS), UMR 6270 CNRS, Université de Rouen

*Dr Didier Marguet, Centre Immunologie Marseille-Luminy (CIML), Inserm, CNRS, Dynamique de la membrane et signalisation du lymphocyte T, Aix Marseille Université

 

 
 Funding