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IQGAP1 Is Important for Activation of Caspase-1 in Macrophages and Is Targeted by Yersinia pestis Type III Effector YopM

Overview of attention for article published in mBio, July 2014
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Title
IQGAP1 Is Important for Activation of Caspase-1 in Macrophages and Is Targeted by Yersinia pestis Type III Effector YopM
Published in
mBio, July 2014
DOI 10.1128/mbio.01402-14
Pubmed ID
Authors

Lawton K. Chung, Naomi H. Philip, Valentina A. Schmidt, Antonius Koller, Till Strowig, Richard A. Flavell, Igor E. Brodsky, James B. Bliska

Abstract

YopM is a leucine-rich repeat (LRR)-containing effector in several Yersinia species, including Yersinia pestis and Y. pseudotuberculosis. Different Yersinia strains encode distinct YopM isoforms with variable numbers of LRRs but conserved C-terminal tails. A 15-LRR isoform in Y. pseudotuberculosis YPIII was recently shown to bind and inhibit caspase-1 via a YLTD motif in LRR 10, and attenuation of YopM(-) YPIII was reversed in mice lacking caspase-1, indicating that caspase-1 inhibition is a major virulence function of YopM(YPIII). To determine if other YopM proteins inhibit caspase-1, we utilized Y. pseudotuberculosis strains natively expressing a 21-LRR isoform lacking the YLTD motif (YopM(32777)) or ectopically expressing a Y. pestis 15-LRR version with a functional (YopM(KIM)) or inactivated (YopM(KIM) D271A) YLTD motif. Results of mouse and macrophage infections with these strains showed that YopM(32777), YopM(KIM), and YopM(KIM) D271A inhibit caspase-1 activation, indicating that the YLTD motif is dispensable for this activity. Analysis of YopM(KIM) deletion variants revealed that LRRs 6 to 15 and the C-terminal tail are required to inhibit caspase-1 activation. YopM(32777), YopM(KIM), and YopM(KIM) deletion variants were purified, and binding partners in macrophage lysates were identified. Caspase-1 bound to YopM(KIM) but not YopM(32777). Additionally, YopM(KIM) bound IQGAP1 and the use of Iqgap1(-/-) macrophages revealed that this scaffolding protein is important for caspase-1 activation upon infection with YopM(-) Y. pseudotuberculosis. Thus, while multiple YopM isoforms inhibit caspase-1 activation, their variable LRR domains bind different host proteins to perform this function and the LRRs of YopM(KIM) target IQGAP1, a novel regulator of caspase-1, in macrophages.

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Mendeley readers

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The data shown below were compiled from readership statistics for 47 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Germany 2 4%
Madagascar 1 2%
Norway 1 2%
Unknown 43 91%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 14 30%
Researcher 9 19%
Student > Doctoral Student 5 11%
Student > Bachelor 3 6%
Student > Master 3 6%
Other 6 13%
Unknown 7 15%
Readers by discipline Count As %
Agricultural and Biological Sciences 17 36%
Immunology and Microbiology 9 19%
Biochemistry, Genetics and Molecular Biology 8 17%
Engineering 2 4%
Decision Sciences 1 2%
Other 3 6%
Unknown 7 15%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 27 May 2016.
All research outputs
#15,169,543
of 25,373,627 outputs
Outputs from mBio
#5,120
of 6,507 outputs
Outputs of similar age
#122,796
of 242,345 outputs
Outputs of similar age from mBio
#66
of 98 outputs
Altmetric has tracked 25,373,627 research outputs across all sources so far. This one is in the 38th percentile – i.e., 38% of other outputs scored the same or lower than it.
So far Altmetric has tracked 6,507 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 25.0. This one is in the 19th percentile – i.e., 19% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 242,345 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 47th percentile – i.e., 47% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 98 others from the same source and published within six weeks on either side of this one. This one is in the 31st percentile – i.e., 31% of its contemporaries scored the same or lower than it.