| RRC ID |
56895
|
| Author |
Arasaki K, Mikami Y, Shames SR, Inoue H, Wakana Y, Tagaya M.
|
| Title |
Legionella effector Lpg1137 shuts down ER-mitochondria communication through cleavage of syntaxin 17.
|
| Journal |
Nat Commun
|
| Abstract |
During infection of macrophages, the pathogenic bacterium Legionella pneumophila secretes effector proteins that induce the conversion of the plasma membrane-derived vacuole into an endoplasmic reticulum (ER)-like replicative vacuole. These ER-like vacuoles are ultimately fused with the ER, where the pathogen replicates. Here we show that the L. pneumophila effector Lpg1137 is a serine protease that targets the mitochondria and their associated membranes. Lpg1137 binds to and cleaves syntaxin 17, a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein that is known to participate in the regulation of mitochondrial dynamics through interaction with the mitochondrial fission factor Drp1 in fed cells and in autophagy through interaction with Atg14L and other SNAREs in starved cells. Cleavage of syntaxin 17 inhibits not only autophagy but also staurosporine-induced apoptosis occurring in a Bax, Drp1-dependent manner. Thus, L. pneumophila can shut down ER-mitochondria communication through cleavage of syntaxin 17.
|
| Volume |
8
|
| Pages |
15406
|
| Published |
2017-5-15
|
| DOI |
10.1038/ncomms15406
|
| PII |
ncomms15406
|
| PMID |
28504273
|
| PMC |
PMC5440676
|
| MeSH |
Animals
Apoptosis
Autophagy
Bacterial Proteins / metabolism*
Endoplasmic Reticulum / microbiology*
HEK293 Cells
HeLa Cells
Humans
Immunoprecipitation
Legionella pneumophila / metabolism*
Macrophages / metabolism
Macrophages / microbiology*
Mice
Mice, Inbred C57BL
Mitochondria / metabolism*
Mutation
Qa-SNARE Proteins / metabolism*
RNA Interference
SNARE Proteins / metabolism
Subcellular Fractions
|
| IF |
11.878
|
| Times Cited |
27
|
| Resource |
| Human and Animal Cells |
HeLa(RCB0007)
THP1(RCB1189) |
