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 research activity concerns molecular mechanisms controlling (neuro)hormone secretion in physiological and pathophysiological conditions. Our group focus its attention on the identification of molecular actorsregulating the biogenesis of dense-core secretory granules, organelles involved in the storing and release of (neuro)hormones in (neuro)endocrine cells. These organelles are generated by budding from the trans-Golgi network membrane, a cell compartment where protein (neuro)hormones are targeted to dense-core secretory granules. Our studies revealed (i) that expression of the soluble protein chromogranin A (CgA) in non-endocrine cells induced the formation of vesicular membrane surrounded structures sharing morphological and functional characteristics with dense-core secretory granules, and (ii) that terminal regions of CgA were crucial to hormone targeting (Montero-Hadjadje et al., 2009). Other studies demonstrated that cytoskeletton insures the trafficking of these CgA-containing vesicular structures as it does with dense-core secretory granules (Elias et al., 2012) and that acto-myosin complex is involved in the biogenesis of secretory granules (Delacour-Delestre et al., 2017). Current studies are concentrated on the identification of molecular partners of CgA requested at the TGN membrane to initiate the budding of dense-core secretory granules. To achieve this goal, we established local (with chemist teams: Pr PY. RENARD, COBRA UMR 6014 CNRS; Dr S. ALEXANDRE, PBS UMR 6270 CNRS) and national (with biochemists: Dr N. VITALE, UPR 3212 CNRS, Strasbourg ; with biophysician: Dr D. MARGUET, CIML, Marseille) collaborations, and we obtained grants from Région Normandie, France-Bioimaging network and Fondation pour la Recherche Médicale. We are currently developing molecular tools (lipid probes), commercially unvailable and that will be used with advanced imaging techniques (TIRF and STED microscopy available on PRIMACEN, the Cell Imaging Plateform of our IRIB Institute; atomic force microscopy available in PBS laboratory; a microscope equipped with a decaging system available in UPR 3212 CNRS; fluorescence correlative spectroscopy available in CIML, Marseille) to identify the role of CgA interaction with membrane lipid partners in neurosecretion regulation in healthy and tumoral (neuro)endocrine cells.

 

Indeed, several (neuro)endocrine cancers are associated to a disrupted hormone secretion suggesting an alteration of secretion mechanisms. Although a massive release of hormones is well kown by clinicians in this pathological context, the molecular mechanisms leading to this dysregulation are poorly investigated. Then, the main goal of our research is to identify the molecular machinery controlling hormone secretion to understand the impact of secretory activity of tumoral (neuro)endocrine cells on the initiation and/or the evolution of (neuro)endocrine cancers  and to consider potential adapted therapeutical applications.

 

 Selected Publications

 

Montero-Hadjadje M., Vaudry H., Turquier V., Leprince J., Do Régo J.L., Yon L., Gallo-Payet N., Plouin P.F., Anouar Y. (2002) Localization and characterization of evolutionary conserved chromogranin A-derived peptides in the rat and human pituitary and adrenal glands. Cell and Tissue Research, 310:223-236. 

 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.

 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.

 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.

 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.

 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. ActaPhysiologica, 192:309-324.

 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.

 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.

 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.

 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.

 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.

 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.

 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.

 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.

 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.


 

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

 

 

 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

 

    

 

   

 

    

 

Current Group Members

  

Maite Montero-Hadjadje, Professor
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Lydie Jeandel, Associate Professor
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Lina Riachy, Post-Doc
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Ophelie Carmon, Ph.D. Student
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Fanny Laguerre, Ph.D. Student
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