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Ras inhibitor CAPRI enables neutrophil-like cells to chemotax through a higher-concentration range of gradients.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2021 Oct 26; Vol. 118 (43). - Publication Year :
- 2021
-
Abstract
- 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 <superscript>kd</superscript> ) exhibit chemoattractant-induced, nonadaptive Ras activation; significantly increased phosphorylation of AKT, GSK-3α/3β, and cofilin; and excessive actin polymerization. capri <superscript>kd</superscript> 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.<br />Competing Interests: The authors declare no competing interest.
- Subjects :
- Actins immunology
Cell Movement
Cell Polarity
Gene Knockdown Techniques
HL-60 Cells
Humans
N-Formylmethionine Leucyl-Phenylalanine pharmacology
Neutrophil Activation drug effects
Neutrophil Activation genetics
Neutrophil Activation immunology
Neutrophils drug effects
Neutrophils physiology
Receptors, G-Protein-Coupled immunology
Shelterin Complex immunology
Signal Transduction
Telomere-Binding Proteins immunology
ras GTPase-Activating Proteins deficiency
ras GTPase-Activating Proteins genetics
ras Proteins immunology
Chemotaxis, Leukocyte immunology
Neutrophils immunology
ras GTPase-Activating Proteins immunology
ras Proteins antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 118
- Issue :
- 43
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 34675073
- Full Text :
- https://doi.org/10.1073/pnas.2002162118