4 May 2016

Role of autophagy as a response to membrane damages: Shigella and Coxiella

In collaboration with P. Sansonetti, Inserm U786 , Institut Pasteur, Paris; Maria-Isabel Colombo (Univ. Mendoza, Argentina)

In collaboration with I Paz and P Sansonetti, we have shown that vacuolar rupture is associated with the recruitment of galectin-3 on glycosylated motifs of cell surface proteins that are exposed to the cytoplasm after the membrane damage (Paz et al., 2010). We have shown that this marker is associated with a massive ubiquitination and the recruitment of the p62 adapter and of LC3, a hallmark of autophagy (Dupont et al., 2009). These results were confirmed and extended by the group of F Randow (MRC, Cambridge, UK) showing that on top of galectin-3, galectin-9 and -8 were also recruited with that latter binding LC3 (Thurston et al., Nature 2012). Targeting membrane remnants to autophagy leads to dampen the danger signals consecutive to the membrane stress caused by the vacuolar rupture (Dupont et al, 2010). This process has an impact on the immune response triggered by infection (Faure & Lafont, 2013).

In collaboration with M-I Colombo, we study the role played by autophagy in the mechanism of Coxiella vacuolar repair extending the concept of the autophagy response to membrane damages.

Nicolas Dupont, Sandra Lacas-Gervais, Nassima Temime-Smaali, Laure-Anne Ligeon

Financial support: French Minister of Research, programs from the National research Agency: Microbiology 2005 & MIE 2009 (Coord. FL), CNRS (PICS).

-Dupont N, Lacas-Gervais S, Bertout J, Paz I, Freche B, Van Nhieu GT, van der Goot FG, Sansonetti PJ, Lafont F. Shigella phagocytic vacuolar membrane remnants participate in the cellular response to pathogen invasion and are regulated by autophagy. Cell Host Microbe. 2009 Aug 20;6(2):137-49.

-Paz I, Sachse M, Dupont N, Cederfur C, Enninga J, Leffler H, Poirier F, Prevost MC, Lafont F, Sansonetti P. Galectin-3, a marker for vacuole lysis by invasive pathogens. Cell Microbiol. 2010 12 :530-544.

-Dupont N., N. Temime-Smaali and F Lafont How ubiquitination and autophagy participate in the regulation of the cell response to bacterial infection Biology of the Cell 2010 102:621-634

-Ligeon L-A., N. Temime-Smaali and F Lafont Ubiquitylation and autophagy in the control of bacterial infections and related inflammatory responses Cellular Microbiol. 2011 13:1303-1311

– Faure M. and F. Lafont Pathogen-Induced Autophagy Signaling in Innate Immunity J Innate Immunity 5:456-470.