Estrogens, Gene Expression and Central Nervous System Pathologies

Université de Franche-Comté
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 - Besancon
Site web - -
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)

Research themes

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).

Descriptive figure

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

Publications

-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.