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Drug
Enzyme
Compound
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Target Concepts:
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Query: UNIPROT:P17931 (
galectin-3
)
2,860
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Gram-negative bacterial pathogens utilize virulence-associated secretion systems to inject, or translocate, effector proteins into host cells to manipulate cellular processes and promote bacterial replication. However, translocated bacterial products are sensed by
n
ucleotide binding domain and
l
eucine-rich
r
epeat-containing proteins (NLRs), which trigger the formation of a multiprotein complex called the inflammasome, leading to secretion of interleukin-1 (IL-1) family cytokines, pyroptosis, and control of pathogen replication. Pathogenic
Yersinia
bacteria inject effector proteins termed Yops, as well as pore-forming proteins that comprise the translocon itself, into target cells. The
Yersinia
translocation regulatory protein YopK promotes bacterial virulence by limiting hyperinjection of the translocon proteins YopD and YopB into cells, thereby limiting cellular detection of
Yersinia
virulence activity. How hyperinjection of translocon proteins leads to inflammasome activation is currently unknown. We found that translocated YopB and YopD colocalized with the late endosomal/
lysosomal protein
LAMP1 and that the frequency of YopD and LAMP1 association correlated with the level of caspase-1 activation in individual cells. We also observed colocalization between YopD and
Galectin-3
, an indicator of endosomal membrane damage. Intriguingly, YopK limited the colocalization of
Galectin-3
with YopD, suggesting that YopK limits the induction or sensing of endosomal membrane damage by components of the type III secretion system (T3SS) translocon. Furthermore, guanylate binding proteins (GBPs) encoded on chromosome 3 (
Gbp
Chr3
), which respond to pathogen-induced damage or alteration of host membranes, were necessary for inflammasome activation in response to hyperinjected YopB/-D. Our findings indicate that lysosomal damage by
Yersinia
translocon proteins promotes inflammasome activation and implicate GBPs as key regulators of this process.
...
PMID:Guanylate Binding Proteins Regulate Inflammasome Activation in Response to Hyperinjected Yersinia Translocon Components. 2878 30
