The TBK1 adaptor and autophagy receptor NDP52 restricts the proliferation of ubiquitin-coated bacteria (Nat Immunol, 2009, 10:1215-1221)

報告日期: 2010/03/16
報告時間: 17:10/18:00
報告學生: 胡佳雯(英文報告)
講評老師: 林以行
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/990316-3.pdf

The TBK1 adaptor and autophagy receptor NDP52 restricts the proliferation of ubiquitin-coated bacteria

Nature Immunology 10, 1215-1221 (2009)

 

Speaker:胡佳雯

Commentator:林以行 老師

Time: 2010/3/16 17:10-18:00

Place: Room 602

 

Abstract:

    TBK1, a member of the IKK family, has been suggested to control the vacuolar integrity during intracellular bacterial infection. In TBK1-deficient cells, the intracellular bacteria can escape from vacuoles into cytosol. Ubiquitination is a protein modification used by cells to label proteins for proteasomal degradation. Recent studies indicated that the ubiquitination system also plays a role in the recognition of bacteria in the cytosol of mammalian cells when the polyubiquitinated proteins accumulate on the surface of salmonella. As a cell-autonomous defense mechanism, autophagy contributes to restrict the pathogens that attempt to invade the cytosol. The interaction between ubiquitinated bacteria to autophagosome is also not clear. In this paper, the authors are interested in the role of TBK1 on the detection of ubiquitin coated bacteria and targeting them for destruction by the autophagy pathway. The TBK1-binding proteins Nap1 and Sintbad colocalized with ubiquitin-coated salmonella, but did not bind ubiquitin directly, which suggested that there must be adaptor proteins that link the TBK1-binding protein Nap1 and Sintbad to ubiquitinated bacteria. The protein as NDP52 was identified that recruits TBK1 to ubiquitin-coated salmonella and bridges ubiquitin and TBK1 complexes. NDP52 is important for restricting the cytosolic replication of salmonella and delivers the salmonella into autophagosomes. The LC3 accumulated around the NDP52-positive bacteria. These finding suggest that the host cells use the ubiquitin system and NDP52 to stimulate autophagy machinery against bacteria attempting to colonize in the cytosol.

 

References:

1.    Perrin, A.J., Jiang, X., Birmingham, C.L., So, N.S. & Brumell, J.H. Recognition of bacteria in the cytosol of mammalian cells by the ubiquitin system. Curr. Biol. 14, 806-811 (2004).

2.    Radtke, A.L. & O’Riordan, M.X. Homeostatic maintenance of pathogen-containing vacuoles requires TBK1-dependent regulation of aquaporin-1. Cell. Microbiol. 10, 2197-2207 (2008).