SNARE mediates autophagosome–lysosome fusion

Publication date: May 2012 Source:Journal of Oral Biosciences, Volume 54, Issue 2 Author(s): Nobumichi Furuta , Atsuo Amano Autophagy is an intracellular bulk degradation/recycling system that turns over cellular constituents. This system has also been shown to play a crucial role in host defense, termed antimicrobial autophagy (xenophagy), in which it functions to degrade intracellular foreign microbial invaders. Xenophagosomes undergo a stepwise maturation process that consists of fusion with lysosomes, after which the cargo undergoes degradation. We have previously shown that intracellular group A Streptococcus (GAS) is captured by xenophagosomes termed GAS-containing autophagosome-like vacuoles (GcAVs), where GAS organisms are degraded following fusion with lysosomes. Our recent investigations have shown that endocytic soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) are involved in the fusion of xenophagosomes and lysosomes. Confocal microscopic analysis has shown that SNAREs, including VAMP8 and Vti1b, colocalize with GFP-LC3 in GcAVs. Our findings also suggested that Vti1b is derived from autophagic compartments, whereas VAMP8 originates from lysosomes. Knockdown of the combinational SNARE proteins VAMP8 and Vti1b with siRNAs disturbed the autophagic fusion of xenophagosomes with lysosomes, and cellular bactericidal efficiency significantly diminished. Furthermore, knockdown of these SNAREs inhibited the fusion of canonical autophag...
Source: Journal of Oral Biosciences - Category: Biomedical Science Source Type: research