RRC ID 38115
著者 Kobayashi S, Koujin T, Kojidani T, Osakada H, Mori C, Hiraoka Y, Haraguchi T.
タイトル BAF is a cytosolic DNA sensor that leads to exogenous DNA avoiding autophagy.
ジャーナル Proc Natl Acad Sci U S A
Abstract Knowledge of the mechanisms by which a cell detects exogenous DNA is important for controlling pathogen infection, because most pathogens entail the presence of exogenous DNA in the cytosol, as well as for understanding the cell's response to artificially transfected DNA. The cellular response to pathogen invasion has been well studied. However, spatiotemporal information of the cellular response immediately after exogenous double-stranded DNA (dsDNA) appears in the cytosol is lacking, in part because of difficulties in monitoring when exogenous dsDNA enters the cytosol of the cell. We have recently developed a method to monitor endosome breakdown around exogenous materials using transfection reagent-coated polystyrene beads incorporated into living human cells as the objective for microscopic observations. In the present study, using dsDNA-coated polystyrene beads (DNA-beads) incorporated into living cells, we show that barrier-to-autointegration factor (BAF) bound to exogenous dsDNA immediately after its appearance in the cytosol at endosome breakdown. The BAF(+) DNA-beads then assembled a nuclear envelope (NE)-like membrane and avoided autophagy that targeted the remnants of the endosome membranes. Knockdown of BAF caused a significant decrease in the assembly of NE-like membranes and increased the formation of autophagic membranes around the DNA-beads, suggesting that BAF-mediated assembly of NE-like membranes was required for the DNA-beads to evade autophagy. Importantly, BAF-bound beads without dsDNA also assembled NE-like membranes and avoided autophagy. We propose a new role for BAF: remodeling intracellular membranes upon detection of dsDNA in mammalian cells.
巻・号 112(22)
ページ 7027-32
公開日 2015-6-2
DOI 10.1073/pnas.1501235112
PII 1501235112
PMID 25991860
PMC PMC4460496
MeSH Autophagy / physiology* Blotting, Western DNA / metabolism* DNA-Binding Proteins / metabolism* Endosomes / metabolism* Fluorescent Antibody Technique, Indirect HeLa Cells Humans Intracellular Membranes / metabolism* Microscopy, Electron Microscopy, Fluorescence Microspheres Nuclear Proteins / metabolism* RNA, Small Interfering / genetics Time-Lapse Imaging
IF 9.412
引用数 16
WOS 分野 CELL BIOLOGY
リソース情報
ヒト・動物細胞 HeLa(RCB0007)