Ras inhibitor CAPRI enables neutrophil-like cells to chemotax through a higher-concentration range of gradients.
Proc Natl Acad Sci U S A
; 118(43)2021 10 26.
Article
en En
| MEDLINE
| ID: mdl-34675073
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 (caprikd ) exhibit chemoattractant-induced, nonadaptive Ras activation; significantly increased phosphorylation of AKT, GSK-3α/3ß, and cofilin; and excessive actin polymerization. caprikd 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.
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Base de datos:
MEDLINE
Asunto principal:
Quimiotaxis de Leucocito
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Proteínas ras
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Proteínas Activadoras de ras GTPasa
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Neutrófilos
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2021
Tipo del documento:
Article