Ras inhibitor CAPRI enables neutrophil-like cells to chemotax through a higher-concentration range of gradients

Neutrophils sense and migrate through an enormous range of che-moattractant gradients through adaptation. Here, we reveal that in human neutrophils, calcium-promoted Ras inactivator (CAPRI) locally controls the GPCR-stimulated Ras adaptation. Human neu-trophils lacking CAPRI (capri(kd)) exhibit chemoattractant-induced, nonadaptive Ras activation; significantly increased phosphoryla-tion of AKT, GSK-3 alpha/3 beta, and cofilin; and excessive actin polymeri-zation. capri(kd) cells display defective chemotaxis in response to high-concentration gradients but exhibit improved chemotaxis in low-or subsensitive-concentration gradients of various chemoat-tractants, 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.

Automated summary

The study demonstrates the important role of CAPRI in mediating GPCR activation-induced Ras adaptation in human neutrophils. By reducing cell sensitivity, CAPRI enables neutrophils to chemotax through higher concentration gradients of chemoattractants.