Estrogènes, Expression Génique et Pathologies du Système Nerveux Central, Besançon – February 2015 CFATG
Estrogènes, Expression Génique et Pathologies du Système Nerveux Central, Besançon – February 2015
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Team EA3922 Laboratory of Biochemistry and Molecular Biology

Université de Franche-Comté
UFR Sciences et Techniques /Laboratoire Biochimie Biologie moléculaire
EA3922 « Estrogènes, Expression Génique et Pathologies du Système Nerveux Central »
SFR IBCT FED 4234
16, route de Gray
Bâtiment DF
25030 BESANCON

Presentation of the team

Web site: http://e2snc.free.fr

Our team EA3922 is located on two sites in Besançon (Laboratory of Biochemistry, UFR of Sciences and Technology and the Laboratory of Histology, Hauts de Chazal, UFR of Medical and Pharmaceutical Sciences, University Hospital Minjoz) sites where we develop two different themes:

    1. 1) In the laboratory located in Hauts de Chazal, our team focuses on the roles of MCH protein in the mouse brain and the regulatory mechanisms of hunger and satiety.
    1. 2) In the laboratory of Biochemistry, we are interested in the problem of cellular stress and metabolism regulating autophagy and specifically the role of the ATG8 family proteins in regulating this process. These studies are conducted in healthy and tumor tissues, one of our main models being breast cancer (projects that we will detail further below).

Team leader

Delage-Mourroux Régis, PR,
Email : regis.delage-mourroux@univ-fcomte.fr

Team members, 2014

Team-Fev2015
From left to right: Aurore Taupin-Claude (doctorante), Eric Hervouet (MCF), Régis Delage-Mourroux (PR), Gilles Despouy (MCF), Laura Perez-Poillet (Doctorante), Raoudha Kacem (Post-doctorante), Michael Boyer-Guittaut (PR), Annick Fraichard (MCF), Valérie Perez (Technicienne), Pascale Adami (MCF)

Keywords

ATG8 Family proteins (LC3, GABARAPL1), Selective autophagy, mitophagy, gene regulation and epigenetic regulation of autophagy genes, breast cancer.

ResearchTopic

From an historical point of view, our team specifically study the functions ofGABARAPL1protein during the course of autophagy because this protein was discovered by our team in 1993 (protein previously known as GEC1) and we have previously shown, for the first time, his role in autophagy in 2010. We also showed in 2010 that a strong expression of GABARAPL1 transcripts is a good prognosis factor for patients with breast cancers, that GABARAPL1 inhibits MCF-7 cancer cell proliferation and that its inhibition alters mitochondrial homeostasis because of the deregulation of autophagic flux inMDA-MB436 cells.
The GABARAPL1 gene is the most regulated gene in the ATG8 family genes and therefore we postulate that this protein might present a specific role in selective autophagy in response to specific metabolic stress, or in defined tissues or diseases. GABARAPL1was described by our team and other laboratories to play an important role in selective autophagy of mitochondria, called mitophagy. Furthermore, this protein is also involved in other cellular processes such as transport of neuronal receptors (GABAAR, ΚOR) at the plasma membrane or microtubule polymerization.
Currently, we are pursuing several projects to understand:
a) The role of proteins of the ATG8 family, including GABARAPL1, during induced and selective autophagy ;
b) The epigenetic regulation of autophagy gene expression in disease models (breast cancer);
c) The role of autophagy proteins in the processes of tumorigenesis and tumor progression;
d) We are also developing the technology of Proximity Ligation Assay (PLA) to study in cellulo protein interactions of autophagy proteins in response to various cellular stresses (see figure 1).

Fig-Fev2015
Figure 1 : Etude par la technique ProximityLigationAssay (PLA) des interactions P62/LC3B en présence (BafA1) ou non (Ct) de Bafilomycine A1.
Figure 2 : Etude par immunofluorescence de la localisation de GABARAPL1(GL1) en absence ou en présence de Bafilomycine A1

References

-Boyer-Guittaut M, Poillet L, Liang Q, Bôle-Richard E, Ouyang X, Benavides GA, Chakrama FZ, Fraichard A, Darley-Usmar VM, Despouy G, Jouvenot M, Delage-Mourroux R, Zhang J. (2014) The role of GABARAPL1/GEC1 in autophagic flux and mitochondrial quality control in MDA-MB-436 breast cancer cells. Autophagy, 10(6):986-1003.
-Poillet L, Pernodet N, Boyer-Guittaut M, Adami P, Borg C, Jouvenot M, Delage-Mourroux R, Despouy G. (2014) QSOX1 inhibitsautophagic flux in breast cancer cells. PLoS One, 9(1):e86641.
-Le Grand JN, Bon K, Fraichard A, Zhang J, Jouvenot M, Risold PY, Boyer-Guittaut M, Delage-Mourroux R. (2013) Specific distribution of the autophagic protein GABARAPL1/GEC1 in the developing and adult mouse brain and identification of neuronal populations expressing GABARAPL1/GEC1. PLoS One, 8(5):e63133.
– Seguin-Py S, Lucchi G, Croizier S, Chakrama FZ, Despouy G, Le Grand JN, Ducoroy P, Boireau W, Boyer-Guittaut M, Jouvenot M, Fraichard A, Delage-Mourroux R. (2012) Identification of HSP90 as a new GABARAPL1 (GEC1)-interacting protein. Biochimie. 94(3):748-58.
– Le Grand, JN., Chakrama, FZ., Seguin-Py, S., Fraichard, A., Delage-Mourroux, R., Jouvenot, M., Risold, PY. and Boyer-Guittaut, M. (2011) GABARAPL1 antibodies: target one protein, get one free! Autophagy, (11):1302-7.
– Chakrama, FZ., Seguin-Py, S., Le Grand, JN., Fraichard, A., Delage-Mourroux, R., Despouy, G., Perez, V., Jouvenot, M. and Boyer-Guittaut, M. (2010) GABARAPL1 (GEC1) associates with autophagic vesicles. Autophagy, (4):495-505.
– Berthier, A., Seguin, S., Sasco, AJ., Bobin, JY., De Laroche, G., Datchary, J., Saez, S., Rodriguez-Lafrasse, C.,Tolle, F., Fraichard, A., Boyer-Guittaut, M., Jouvenot, M., Delage-Mourroux, R. and Descotes, F. (2010) High expression of gabarapl1 is associated with a better outcome for patients with lymph node-positive breast cancer. Br J Cancer, 102(6), 1024-31.

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