| Accession |
PRJCA012098 |
| Title |
Wip1_Neu |
| Relevance |
Medical |
| Data types |
Transcriptome or Gene expression
|
| Organisms |
Mus musculus homourus
|
| Description |
Neutrophil extracellular traps (NET) are critical for neutrophils to efficiently respond to infection, however molecular regulation of NET formation remains poorly understood. In the current study, we found that inhibition of the phosphatase wild-type p53-induced phosphatase 1 (Wip1) significantly limited the activity of Staphylococcus aureus (S. aureus) and accelerated abscess healing in an S. aureus-induced abscess mouse model by enhancing NET formation. Wip1 inhibitor significantly enhanced NET formation of mouse and human neutrophils in vitro. High-resolution mass spectrometry and biochemical assays demonstrated that Coro1a is a substrate of Wip1. Further experiments also revealed that Wip1 more favorably directly interacts with phosphorylated Coro1a compared to non-phosphorylated, inactivated Coro1a. The phosphorylated Ser426 site of Coro1a, and the 28-90 aa domain of Wip1, are essential for their direct interaction and Wip1 dephosphorylation of p-Coro1a-Ser426. Wip1 deletion or inhibition in neutrophils significantly upregulated phosphorylation of the Coro1a-Ser426 site, which activated phospholipase C and subsequently the calcium pathway, the latter promoted NET formation after infection or lipopolysaccharide stimulation. This study identified Coro1a as a novel substrate of Wip1 and revealed that Wip1 was a negative regulator of NET formation during infection. These results support the potential application of Wip1 inhibitor to treat bacterial infections. |
| Sample scope |
Monoisolate |
| Release date |
2022-09-23 |
| Publication |
| PubMed ID |
Article title |
Journal name |
DOI |
Year |
| 37386173
|
Wip1 inhibits neutrophil extracellular traps to promote abscess formation in mice by directly dephosphorylating Coronin-1a
|
Cellular & Molecular Immunology
|
10.1038/s41423-023-01057-2
|
2023
|
|
|
| Grants |
| Agency |
program |
Grant ID |
Grant title |
| National Natural Science Foundation of China (NSFC)
|
|
31930041
|
|
|
|
| Submitter |
Zhaoqi
Zhang (zhangzhaoqi@ioz.ac.cn)
|
| Organization |
University of Chinese Academy of Sciences |
| Submission date |
2022-09-23 |
