Galectin 8 targets damaged vesicles for autophagy to defend cells against bacterial invasion

Thurston T. L, Wandel M. P, von Muhlinen N, Foeglein A. and Randow F. Nature. 482(7385): 414-8. (2012).

Speaker: Shu-Ching Lin (林紓晴)                Time: 13:00~14:00, Apr. 18, 2012

Commentator: Dr. Hsiao-Sheng Liu(劉校生老師)       Place: Room 601

Abstract:

Autophagy is a physiological response to combat and target the invasion of pathogens for degradation and target invading pathogens such as Salmonella enterica serovar Typhimurium, however the underlying mechanisms are not well known. When Salmonella invades the cell, it replicates within a vacuolar compartment termed the Salmonella- containing vacuole (SCV). Previous study indicated that galectin 3 accumulates on damaged bacteria-containing vesicles and it is a marker for vacuole lysis by invasive pathogens.¹ Galectins are β-galactoside-binding lectins with conserved carbohydrate recognition domains. Galectin usually accumulates in the cytosol and functions as the danger-recognition receptor under the conditions of lake of complex carbohydrates. After S. Typhimurium invasion, the authors found that galectin 8 binds damaged SCV by recognition of hostglycan. They further revealed that recruitment of galectin 8 to the damaged vesicle was detected not only by S. Typhimurium but also Listeria and Shigella invasion. Furthermore, the vesicle damaged by osmotic stress also induces the recruitment of galectin 8. All together, galectin 8 serves as a versatile receptor for damaged vesicles. Furthermore, galectin 8 activates antibacterial autophagy by recruiting NDP52, an adaptor protein contributing to LC3 recruitment to the pathogen. Galectin 8-dependent recruitment of NDP52 to SCV is transient and followed by ubiquitin-dependent NDP52 recruitment. It indicates that galectin 8 acts as an early signal to induce autophagy. In conclusion, galectin 8 binds carbohydrate and recruits NDP52 followed by LC3, which activates autophagy to degrade the pathogens soon after invasion. Galectin 8 functions as a danger receptor, it helps the host to detect and eliminate invading pathogens by monitoring endosomal and lysosomal integrity on the basis of the specific lake of complex carbohydrates in the cytosol.

References:

1. Paz, I. et al. Galectin-3, a marker for vacuole lysis by invasive pathogens. Cell Microbiol 12, 530-544, doi:10.1111/j.1462-5822.2009.01415.x (2010).

2. Huang, J. et al. A sweet way of sensing danger. Nature 482, 316-317.