Ras inhibitor CAPRI enables neutrophil-like cells to chemotax through a higher-concentration range of gradients.
Xuehua XuXi WenAmer MoosaSmit BhimaniTian JinPublished in: Proceedings of the National Academy of Sciences of the United States of America (2021)
Neutrophils sense and migrate through an enormous range of chemoattractant gradients through adaptation. Here, we reveal that in human neutrophils, calcium-promoted Ras inactivator (CAPRI) locally controls the GPCR-stimulated Ras adaptation. Human neutrophils lacking CAPRI ( capri kd ) exhibit chemoattractant-induced, nonadaptive Ras activation; significantly increased phosphorylation of AKT, GSK-3α/3β, and cofilin; and excessive actin polymerization. capri kd cells display defective chemotaxis in response to high-concentration gradients but exhibit improved chemotaxis in low- or subsensitive-concentration gradients of various chemoattractants, as a result of their enhanced sensitivity. Taken together, our data reveal that CAPRI controls GPCR activation-mediated Ras adaptation and lowers the sensitivity of human neutrophils so that they are able to chemotax through a higher-concentration range of chemoattractant gradients.
Keyphrases
- endothelial cells
- wild type
- induced pluripotent stem cells
- signaling pathway
- high glucose
- genome wide
- induced apoptosis
- single cell
- gene expression
- body mass index
- cell proliferation
- physical activity
- machine learning
- weight loss
- electronic health record
- big data
- pi k akt
- deep learning
- endoplasmic reticulum stress
- cell migration