|Cell Polarity and Migration|
|HEAD||ETIENNE-MANNEVILLE Sandrine / firstname.lastname@example.org|
|MEMBERS||Dr BOEDA Batiste/ JEHANNO Muguette/ Dr PESNEL Emeline/ Dr MZALI Rym/ Dr SAKAMOTO Yasuhisa/ DUPIN Isabelle/ PEGLION Florent
The focus of our labis to decipher the molecular mechanisms controlling cell polarization and migration in health and disease. We study polarization in migrating astrocytes to characterize the signalling pathways involved in the regulation of cell migration. Astrocytes are major glial cells of the central nervous system and they fulfill many different functions allowing the development, survival and functions of neurons. Although immobile in normal situations, astrocytes can become motile in response to inflammatory situations accompanying cerebral lesions, infections or neurogenerative diseases. Astrocyte migration is, in these cases, a key event to define the brain regions accessible to neuronal regeneration. Moreover, astrocytes can give rise to tumors, called gliomas which are characterized by their invasiveness into the brain parenchyma. Their invasive properties render these tumors particulary resistant to classical cancer treatment.
Our goal is to better define the fundamental signalling pathways controlling normal astrocyte polarization and migration during inflammatory situations. We want to determine what are the mechanisms controlling astrocyte migration during inflammatory situation and if alteration of these pathways can lead to the invasive properties of astrocyte-derived tumors. We thereby hope to identify therapeutic targets that will allow a better control of astrocyte migration in various pathological situations. We focus on evolutionary conserved polarity proteins and tumor suppressor genes in sensing polarity cues or in intracellular signalling pathways leading to cytoskeleton and vesicle trafficking regulation.
Some of the current issues being addressed are
In vitro cell polarity and cell migration models- Cell biology and microscopy techniques – Biochemistry - Molecular biology - Global transcriptomic approach of human tumors.
Keywords: Polarity, migration, astrocytes, gliomas, Rho GTPases, tumor suppressor genes, cytoskeleton, microtubules, centrosome
S. Etienne-Manneville, J.-B. Manneville, S. Nicholls , A. Ferenczi, A. Hall. 2005. Cdc42 and Par6-PKC regulate the spatially localized association of Dlg1 and APC to control cell polarization. J.Cell Biol. 170: 895-901.
C. Forcet, S. Etienne-Manneville (Equal contribution), H. Gaude, L. Fournier, S. Debilly, M. Salmi, A. Baas, S. Olschwang, H. Clevers, M. Billaud. 2005. Functional analysis of Peutz-Jeghers mutations reveals that the carboxy-terminal region of LKB1 exerts a crucial role in the control of cell polarity. Hum. Mol. Gen. 14 : 1283-1292
N. Osmani, N. Vitale, J.-P. Borg, S. Etienne-Manneville. 2006. Scrib controls Cdc42 localization and activity to promote cell polarization during astrocyte migration. Curr. Biol. 16:2395-405
S. Etienne-Manneville. Polarity proteins in migration and invasion. 2008. Oncogene. 27(55):6970-80
S. Etienne-Manneville. Polarity proteins in glial cell functions. 2008. Curr. Opin. Neurobiol. 18(5):488-94.
Activity Reports 2009 - Institut Pasteur
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