Caspases regulate VAMP-8 expression and phagocytosis in dendritic cells.
During an inflammation and upon encountering pathogens, immature dendritic cells (DC) undergo a maturation process to become highly efficient in presenting antigens. This transition from immature to mature state is accompanied by various physiological, functional and morphological changes including reduction of caspase activity and inhibition of phagocytosis in the mature DC. Caspases are cysteine proteases which play essential roles in apoptosis, necrosis and inflammation. Here, we demonstrate that VAMP-8, (a SNARE protein of the early/late endosomes) which has been shown previously to inhibit phagocytosis in DC, is a substrate of caspases. Furthermore, we identified two putative conserved caspase recognition/cleavage sites on the VAMP-8 protein. Consistent with the up-regulation of VAMP-8 expression upon treatment with caspase inhibitor (CI), immature DC treated with CI exhibits lower phagocytosis activity. Thus, our results highlight the role of caspases in regulating VAMP-8 expression and subsequently phagocytosis during maturation of DC.
Ho
Yong Hou Sunny
YH
Department of Microbiology, Laboratory of Membrane Trafficking and Immunoregulation, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Republic of Singapore.
Cai
Deyu Tarika
DT
Huang
Dachuan
D
Wang
Cheng Chun
CC
Wong
Siew Heng
SH
D000595:Amino Acid Sequence; D000818:Animals; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D010587:Phagocytosis; D050683:R-SNARE Proteins / Q000096:biosynthesis / Q000378:metabolism*; D015854:Up-Regulation
D061945:Caspase Inhibitors; D008070:Lipopolysaccharides; D050683:R-SNARE Proteins; C491831:Vamp8 protein, mouse; D020169:Caspases